Method for producing MPS-compatible water gradient contact lenses

ABSTRACT

The invention is related to a process for producing contact lenses that not only comprise a water gradient structural configurations, but also have a minimized uptakes of polyquaternium-1 and a long-lasting surface hydrophilicity and wettability even after being undergone a simulated 30-days lens care regime.

This application claims the benefits under 35 USC § 119 (e) of U.S.provisional application Nos. 62/598,018, 62/598,025, 62/598,028,62/598,029, all filed on 13 Dec. 2017, incorporated by references intheir entireties.

The present invention generally relates to a method for producing watergradient contact lenses which are compatible with multi-purpose lenscare solutions (MPS).

BACKGROUND

A new class of soft contact lenses, water gradient silicone hydrogelcontact lenses, have been developed and successfully introduced asdaily-disposable contact lenses, DAILIES® TOTAL1® (Alcon) in the market.This new class of silicone hydrogel contact lenses is characterized byhaving a water-gradient structural configuration, an increase from 33%to over 80% water content from core to surface (U.S. Pat. No.8,480,227). This unique design can deliver a highly-lubricious andextremely-soft, water-rich lens surface that in turn provide superiorwearing comfort to patients. Such soft contact lenses can be producedaccording to a cost-effective approach that is described in U.S. Pat.No. 8,529,057 and involves a step of crosslinking and covalentlyattaching of a water-soluble highly-branched hydrophilic polymericmaterial onto lens surfaces to form surface gels.

According to U.S. Pat. No. 8,529,057, contact lenses having awater-gradient structural configuration and a soft, water-rich, andlubricious surface can be produced by forming an anchoring layer on eachcontact lens by dipping the contact lenses in a coating solution of apolyanionic polymer and then covalently attaching a water-solublehighly-branched hydrophilic polymeric material onto the anchoring layerdirectly in a lens package during autoclave. The water-solublehighly-branched hydrophilic polymeric material is prepared by partiallyreacting a polyamidoamine-epichlorohydrin (PAE) with a wetting agent, atvarious concentration ratio of PAE to the wetting agent and at areaction temperature for a given reaction time, to achieve a desiredlubricity of the surface gels while minimizing or eliminating surfacedefects (e.g., surface cracking, etc.).

Although the newly-developed water-gradient silicone hydrogel contactlenses can provide superior wearing comfort to patients due to theirextremely-soft, water-rich and relatively-thick hydrogel coatings, theymay not be compatible with all lens care solutions in the market. Forinstance, these new contact lenses may not be compatible with somemultipurpose lens care solutions existed in the market, because they arelikely to uptake polycationic antimicrobials (e.g., polyhexamethylenebiguanide, Polyquaternium-1 (aka PolyQuad®), or the like, which arecommonly found in most multipurpose lens care solutions), due to thepresence of the anchoring layer of a polyanionic material. Thosepolycationic antimicrobials adsorbed by the contact lenses may bereleased into the eye and may cause undesirable clinical symptoms insome persons, such as diffuse corneal staining and product intolerance,when the lenses are worn by patients. Because of the incompatibilitywith some multipurpose lens care solutions, the newly-developed watergradient silicone hydrogel contact lenses may not be suitable to be usedas weekly or monthly disposable contact lenses which must be cleaned anddisinfected almost on the daily basis with a lens care solution.

U.S. Pat. App. Nos. 2015/0166205A1 and 2016/0326046A1 disclosesapproaches for reducing water gradient contact lenses' susceptibility todeposition and accumulation of polycationic antimicrobials by adding onestep involving use of a polyamidoamine-epichlorohydrin (PAE). However,there are some disadvantages associated with those approaches. Forexample, although the susceptibility to deposition and accumulation ofpolycationic antimicrobials of a contact lens with a hydrogel coatingcan be reduced according to those approaches, the lubricity, wettabilityand/or hydrophilicity of the resultant contact lens will be reducedsimultaneously and the reduction in deposition and accumulation ofpolycationic antimicrobials may not be sufficient to render the contactlenses compatible with all multipurpose lens care solutions in themarket. Further, the contact lenses obtained according to thoseapproaches may not be able to survive digital rubbings required in thelens care regimes involving a multipurpose lens care solution oraccidental lens inversion during lens manufacturing or handling, becausethe digital rubbings of the contact lenses and lens inversion can causedamages to the hydrogel coating on the contact lenses as evidenced bycracking lines visible under dark field after the contact lens isinversed or rubbed between fingers.

Therefore, there is still a need for a method for producing watergradient contact lenses which are compatible with multipurpose lens caresolutions while having a high resistance to digital rubbings.

SUMMARY OF THE INVENTION

The invention is related to a process for producing contact lenses thatnot only comprise the much desired water gradient structuralconfigurations but also have a significantly reduced polyquaternium-1uptake (“PU”) and a long-lasting surface hydrophilicity and wettabilityeven after being subjected to a 30 days of lens regime involving amultipurpose lens care solution.

Because contact lenses produced according to a process of the inventioncan have the desired water gradient structural configuration and arelatively-thick, extremely-soft and water-rich hydrogel surface layer,they can provide superior wearing comfort. More importantly, theproduced contact lenses are compatible with multipurpose lens caresolutions present in the market and can endure the harsh lens carehandling conditions (e.g., digital rubbings, accidental inversion ofcontact lenses, etc.) encountered in a daily lens care regime. As such,they are suitable to be used as weekly- or monthly-disposable contactlenses.

These and other aspects of the invention will become apparent from thefollowing description of the presently preferred embodiments. Thedetailed description is merely illustrative of the invention and doesnot limit the scope of the invention, which is defined by the appendedclaims and equivalents thereof. As would be obvious to one skilled inthe art, many variations and modifications of the invention may beeffectuated without departing from the spirit and scope of the novelconcepts of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically depicts a sectional view of the structuralconfiguration of a contact lens according to a preferred embodiment ofthe invention.

FIG. 2 schematically depicts a sectional view of the structuralconfiguration of a contact lens according to another preferredembodiment of the invention.

FIG. 3 schematically illustrates a lens holder for performing thesimulated abrasion cycling treatment of a lens in order to determine thelong-lasting lubricity and/or long-lasting wettability of a contact lensof the invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well-known and commonly employed inthe art.

“About” as used herein in this application means that a number, which isreferred to as “about”, comprises the recited number plus or minus 1-10%of that recited number.

“Contact Lens” refers to a structure that can be placed on or within awearer's eye. A contact lens can correct, improve, or alter a user'seyesight, but that need not be the case. A contact lens can be of anyappropriate material known in the art or later developed, and can be ahard lens, a rigid gas permeable lens, a soft lens, or a hybrid lens.

A “hard contact lens” refers a contact lens comprising a hard plastics(e.g., crosslinked polymethylmethacrylate) as bulk (core) material.

A “rigid gas permeable contact lens” refers to a contact lens comprisinga gas permeable material (e.g., a crosslinked polymeric material madefrom fluorosilicone acrylates) as bulk (core) material.

A soft contact lens can be a non-silicone hydrogel lens, a siliconehydrogel lens or a silicone lens. A “hydrogel contact lens” refers to acontact lens comprising a non-silicone hydrogel bulk (core) material. A“silicone hydrogel contact lens” refers to a contact lens comprising asilicone hydrogel bulk (core) material. A “silicone contact lens” refersto a contact lens made of a crosslinked silicone material as its bulk(or core or base) material which has three-dimensional polymer networks(i.e., polymer matrix), is insoluble in water, and can hold less thanabout 7.5% (preferably less than about 5%, more preferably less thanabout 2.5%, even more preferably less than about 1%) by weight of waterwhen fully hydrated.

A hybrid contact lens has a central optical zone that is made of a gaspermeable lens material, surrounded by a peripheral zone made ofsilicone hydrogel or regular hydrogel lens material.

A “hydrogel” or “hydrogel material” refers to a crosslinked polymericmaterial which is insoluble in water, but can hold at least 10 percentby weight of water in its three-dimensional polymer networks (i.e.,polymer matrix) when it is fully hydrated.

As used in this application, the term “non-silicone hydrogel” refers toa hydrogel that is theoretically free of silicon.

As used in this application, the term “silicone hydrogel” refers to ahydrogel containing silicone. A silicone hydrogel typically is obtainedby copolymerization of a polymerizable composition comprising at leastone silicone-containing vinylic monomer or at least onesilicone-containing vinylic macromer or at least one silicone-containingprepolymer having ethylenically unsaturated groups.

“Hydrophilic,” as used herein, describes a material or portion thereofthat will more readily associate with water than with lipids.

A “vinylic monomer” refers to a compound that has one sole ethylenicallyunsaturated group, is soluble in a solvent, and can be polymerizedactinically or thermally.

The term “soluble”, in reference to a compound or material in a solvent,means that the compound or material can be dissolved in the solvent togive a solution with a concentration of at least about 0.05% by weightat room temperature (i.e., from about 22° C. to about 28° C.).

The term “insoluble”, in reference to a compound or material in asolvent, means that the compound or material can be dissolved in thesolvent to give a solution with a concentration of less than 0.005% byweight at room temperature (as defined above).

As used in this application, the term “ethylenically unsaturated group”is employed herein in a broad sense and is intended to encompass anygroups containing at least one >C═C< group. Exemplary ethylenicallyunsaturated groups include without limitation (meth)acryloyl

allyl, vinyl, styrenyl, or other C═C containing groups.

The term “(meth)acrylamide” refers to methacrylamide and/or acrylamide.

The term “(meth)acrylate” refers to methacrylate and/or acrylate.

As used herein, “actinically” in reference to curing, crosslinking orpolymerizing of a polymerizable composition, a prepolymer or a materialmeans that the curing (e.g., crosslinked and/or polymerized) isperformed by actinic irradiation, such as, for example, UV/visibleirradiation, ionizing radiation (e.g. gamma ray or X-ray irradiation),microwave irradiation, and the like. Thermal curing or actinic curingmethods are well-known to a person skilled in the art.

A “hydrophilic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that iswater-soluble or can absorb at least 10 percent by weight of water.

A “hydrophobic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that isinsoluble in water and can absorb less than 10 percent by weight ofwater.

A “blending vinylic monomer” refers to a vinylic monomer capable ofdissolving both hydrophilic and hydrophobic components of apolymerizable composition to form a solution.

An “acrylic monomer” refers to a vinylic monomer having one sole(meth)acryloyl group.

An “N-vinyl amide monomer” refers to an amide compound having a vinylgroup (—CH═CH₂) that is directly attached to the nitrogen atom of theamide group.

A “macromer” or “prepolymer” refers to a compound or polymer comprisingethylenically unsaturated groups and having a number average molecularweight of greater than 700 Daltons.

As used in this application, the term “vinylic crosslinker” refers to acompound having at least two ethylenically unsaturated groups. A“vinylic crosslinking agent” refers to a subclass of vinyliccrosslinkers each having a number average molecular weight of 700Daltons or less.

As used in this application, the term “polymer” means a material formedby polymerizing or crosslinking one or more monomers, macromers,prepolymers and/or combinations thereof.

As used in this application, the term “molecular weight” of a polymericmaterial (including monomeric or macromeric materials) refers to thenumber average molecular weight unless otherwise specifically noted orunless testing conditions indicate otherwise.

A “polysiloxane segment” refers to a polymer chain consisting of atleast three consecutively- and directly-linked siloxane units (divalentradical) each independent of one another having a formula of

in which R₁′ and R₂′ are two substituents independently selected fromthe group consisting of C₁-C₁₀ alkyl, C₁-C₄ alkyl- orC₁-C₄-alkoxy-substituted phenyl, C₁-C₁₀ fluoroalkyl, C₁-C₁₀ fluoroether,C₆-C₁₈ aryl radical, -alk-(OC₂H₄)_(γ1)—OR^(o) (in which alk is C₁-C₆alkyl diradical, R^(o) is H or C₁-C₄ alkyl and γ1 is an integer from 1to 10), a C₂-C₄₀ organic radical having at least one functional groupselected from the group consisting of hydroxyl group (—OH), carboxylgroup (—COOH), —NR₃′R₄′, amino linkages of —NR₃′—, amide linkages of—CONR₃′—, amide of —CONR₃′R₄′, urethane linkages of —OCONH—, and C₁-C₄alkoxy group, or a linear hydrophilic polymer chain, in which R₃′ andR₄′ independent of each other are hydrogen or a C₁-C₁₅ alkyl.

A “polysiloxane vinylic monomer” refers to a compound comprising atleast one polysiloxane segment and one sole ethylenically-unsaturatedgroup.

A “polysiloxane vinylic crosslinker” refers to a compound comprising atleast one polysiloxane segment and at least twoethylenically-unsaturated groups.

A “chain-extended polysiloxane vinylic crosslinker” refers to a compoundcomprising at least two ethylenically-unsaturated groups and at leasttwo polysiloxane segments each pair of which is linked by one divalentradical.

A “polycarbosiloxane” refers to a compound containing at least onepolycarbosiloxane segment which is a polymer chain consisting of atleast three consecutively- and directly-linked siloxane units (divalentradical) each independent of one another having a formula of

in which n1 is an integer of 2 or 3, R₁″, R₂″, R₃″, and R₄″ independentof one another are a C₁-C₆ alkyl radical (preferably methyl).

A “polycarbosiloxane vinylic monomer” refers to a compound comprising atleast one polycarbosiloxane segment and one soleethylenically-unsaturated group.

A “polycarbosiloxane vinylic crosslinker” refers to a compoundcomprising at least one polycarbosiloxane segment and at least twoethylenically-unsaturated groups.

The term “fluid” as used herein indicates that a material is capable offlowing like a liquid.

As used in this application, the term “clear” in reference to apolymerizable composition means that the polymerizable composition is atransparent solution or liquid mixture (i.e., having a lighttransmissibility of 85% or greater in the range between 400 to 700 nm).

The term “alkyl” refers to a monovalent radical obtained by removing ahydrogen atom from a linear or branched alkane compound. An alkyl group(radical) forms one bond with one other group in an organic compound.

The term “alkylene divalent group” or “alkylene diradical” or “alkyldiradical” interchangeably refers to a divalent radical obtained byremoving one hydrogen atom from an alkyl. An alkylene divalent groupforms two bonds with other groups in an organic compound.

The term “alkyl triradical” refers to a trivalent radical obtained byremoving two hydrogen atoms from an alkyl. An alkyl triradical formsthree bonds with other groups in an organic compound.

The term “alkoxy” or “alkoxyl” refers to a monovalent radical obtainedby removing the hydrogen atom from the hydroxyl group of a linear orbranched alkyl alcohol. An alkoxy group (radical) forms one bond withone other group in an organic compound.

As used in this application, the term “amino group” refers to a primaryor secondary amino group of formula —NHR′, where R′ is hydrogen or aC₁-C₂₀ unsubstituted or substituted, linear or branched alkyl group,unless otherwise specifically noted.

In this application, the term “substituted” in reference to an alkyldiradical or an alkyl radical means that the alkyl diradical or thealkyl radical comprises at least one substituent which replaces onehydrogen atom of the alkyl diradical or the alkyl radical and isselected from the group consisting of hydroxy (—OH), carboxy (—COOH),—NH₂, sulfhydryl (—SH), C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio(alkyl sulfide), C₁-C₄ acylamino, C₁-C₄ alkylamino, di-C₁-C₄ alkylamino,halogen atom (Br or Cl), and combinations thereof.

In this application, an “oxazoline” refers to a compound of

in which: R¹ is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl,N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or a monovalent radical of-alk-(OC₂H₄)_(m3)—OR″ in which alk is C₁-C₄ alkyl diradical; R″ is C₁-C₄alkyl (preferably methyl); and m3 is an integer from 1 to 10 (preferably1 to 5).

In this application, the term “polyoxazoline” refers to a polymer orpolymer segment of

in which: R¹ is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl,N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or a monovalent radical of-alk-(OC₂H₄)₃—OR″ in which alk is C₁-C₄ alkyl diradical; R″ is C₁-C₄alkyl (preferably methyl); m3 is an integer from 1 to 10 (preferably 1to 5); x is an integer from 5 to 500.

In this application, the term “poly(2-oxazoline-co-ethyleneimine)”refers to a statistical copolymer or a polymer segment thereof having aformula of

in which: R¹ is hydrogen, methyl, ethyl, N-pyrrolidonylmethyl,N-pyrrolidonylethyl, N-pyrrolidonylpropyl, or a monovalent radical of-alk-(OC₂H₄)_(m3)—OR″ in which alk is C₁-C₄ alkyl diradical; R″ is C₁-C₄alkyl (preferably methyl); m3 is an integer from 1 to 10 (preferably 1to 5); x is an integer from 5 to 500; z is an integer equal to or lessthan x. A poly(2-oxazoline-co-ethyleneimine) is obtained by hydrolyzinga polyoxazoline.

In this application, the term“poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin” refers to a polymerobtained by reacting a poly(2-oxazoline-co-ethyleneimine) withepichlorohydrin to convert all or substantial percentage (≥90%) of thesecondary amine groups of the poly(2-oxazoline-co-ethyleneimine) intoazetidinium groups. Examples ofpoly(2-oxazoline-co-ethyleneimine)-epichlorohydrin are disclosed in U.S.pat. Appl. Pub. No. 2016/0061995A1.

An “epichlorohydrin-functionalized polyamine” or“epichlorohydrin-functionalized polyamidoamine” refers to a polymerobtained by reacting a polyamine or polyamidoamine with epichlorohydrinto convert all or a substantial percentage of the secondary amine groupsof the polyamine or polyamidoamine into azetidinium groups.

The term “polyamidoamine-epichlorohydrn” refers to anepichlorohydrin-functionalized adipic acid-diethylenetriamine copolymer.

In this application the term “azetidinium” or “3-hydroxyazetidinium”refers to a positively-charged, divalent radical (or group or moiety) of

The term “thermally-crosslinkable” in reference to a polymeric materialor a functional group means that the polymeric material or thefunctional group can undergo a crosslinking (or coupling) reaction withanother material or functional group at a relatively-elevatedtemperature (from about 40° C. to about 140° C.), whereas the polymericmaterial or functional group cannot undergo the same crosslinkingreaction (or coupling reaction) with another material or functionalgroup at a temperature of from about 5° C. to about 15° C., to an extenddetectable for a period of about one hour.

The term “azlactone” refers to a mono-valent radical of formula

in which p is 0 or 1; ³R and ⁴R independently of each other is C₁-C₈alkyl (preferably methyl).

The term “aziridine group” refers to a mono-valent radical of formula

in which R1 is hydrogen, methyl or ethyl.

As used in this application, the term “phosphorylcholine” refers to azwitterionic group of

in which n is an integer of 1 to 5 and R₁, R₂ and R₃ independently ofeach other are C₁-C₈ alkyl or C₁-C₈ hydroxyalkyl.

As used in this application, the term “reactive vinylic monomer” refersto any vinylic monomer having at least one reactive functional groupselected from the group consisting of carboxyl group, primary aminogroup, and secondary amino group.

As used in this application, the term “non-reactive vinylic monomer”refers to any vinylic monomer (either hydrophilic or hydrophobic vinylicmonomer) free of carboxyl group, primary amino group, secondary aminogroup, epoxide group, isocyanate group, azlactone group, or aziridinegroup.

A free radical initiator can be either a photoinitiator or a thermalinitiator. A “photoinitiator” refers to a chemical that initiates freeradical crosslinking/polymerizing reaction by the use of light. A“thermal initiator” refers to a chemical that initiates radicalcrosslinking/polymerizing reaction by the use of heat energy.

A “spatial limitation of actinic radiation” refers to an act or processin which energy radiation in the form of rays is directed by, forexample, a mask or screen or combinations thereof, to impinge, in aspatially restricted manner, onto an area having a well-definedperipheral boundary. A spatial limitation of UV radiation is obtained byusing a mask or screen having a radiation (e.g., UV) permeable region, aradiation (e.g., UV) impermeable region surrounding theradiation-permeable region, and a projection contour which is theboundary between the radiation-impermeable and radiation-permeableregions, as schematically illustrated in the drawings of U.S. Pat. Nos.6,800,225 (FIGS. 1-11), and 6,627,124 (FIGS. 1-9), 7,384,590 (FIGS.1-6), and 7,387,759 (FIGS. 1-6). The mask or screen allows to spatiallyprojects a beam of radiation (e.g., UV radiation) having across-sectional profile defined by the projection contour of the mask orscreen. The projected beam of radiation (e.g., UV radiation) limitsradiation (e.g., UV radiation) impinging on a lens formulation locatedin the path of the projected beam from the first molding surface to thesecond molding surface of a mold. The resultant contact lens comprisesan anterior surface defined by the first molding surface, an oppositeposterior surface defined by the second molding surface, and a lens edgedefined by the sectional profile of the projected UV beam (i.e., aspatial limitation of radiation). The radiation used for thecrosslinking is radiation energy, especially UV radiation, gammaradiation, electron radiation or thermal radiation, the radiation energypreferably being in the form of a substantially parallel beam in orderon the one hand to achieve good restriction and on the other handefficient use of the energy.

The intrinsic “oxygen permeability”, Dk_(i), of a material is the rateat which oxygen will pass through a material. In this application, theterm “oxygen permeability (Dk)” in reference to a hydrogel (silicone ornon-silicone) or a contact lens means a corrected oxygen permeability(Dk_(c)) which is measured at about 34-35° C. and corrected for thesurface resistance to oxygen flux caused by the boundary layer effectaccording to the procedures described in Example 1 of U.S. Pat. Appl.Pub. No. 2012/0026457 A1. Oxygen permeability is conventionallyexpressed in units of barrers, where “barrer” is defined as [(cm³oxygen)(mm)/(cm²)(sec)(mm Hg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

“Ophthalmically compatible”, as used herein, refers to a material orsurface of a material which may be in intimate contact with the ocularenvironment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.

The term “ophthalmically safe” with respect to a packaging solution forsterilizing and storing contact lenses is meant that a contact lensstored in the solution is safe for direct placement on the eye withoutrinsing after autoclave and that the solution is safe and sufficientlycomfortable for daily contact with the eye via a contact lens. Anophthalmically-safe packaging solution after autoclave has a tonicityand a pH that are compatible with the eye and is substantially free ofocularly irritating or ocularly cytotoxic materials according tointernational ISO standards and U.S. FDA regulations.

As used in this application, the term “water gradient” in reference to acontact lens means that there is an increase in water content observedin passing from the core to the surface of the contact lens, reachingthe highest water content in the region near and including the surfaceof the contact lens. It is understood that the increase in water contentfrom the core to the surface of the contact lens can be continuousand/or step-wise, so long as the water content is highest in the regionnear and including the surface of the contact lens.

The term “modulus” or “elastic modulus” in reference to a contact lensor a material means the tensile modulus or Young's modulus which is ameasure of the stiffness of a contact lens or a material. The moduluscan be measured using a method in accordance with ANSI Z80.20 standard.A person skilled in the art knows well how to determine the elasticmodulus of a silicone hydrogel material or a contact lens. For example,all commercial contact lenses have reported values of elastic modulus.

As used in this application, the term “inner layer” or “bulk material”in reference to a contact lens interchangeably means a layer that has a3-dimensional shape of a contact lens and includes a central curvedplane (which divides the contact lens into two parts, one containing theanterior surface and the other containing the posterior surface) and hasa variable thickness.

As used in this application, the term “outer surface hydrogel layer” inreference to a contact lens means an outmost hydrogel layer on thesurface of the contact lens, which consists of an anterior outerhydrogel layer and a posterior outer hydrogel layer and which fullycovers the inner layer (or lens bulk material).

As used in this application, the term “anterior outer hydrogel layer” inreference to a contact lens means a hydrogel layer that includes theanterior surface of the contact lens, is substantially uniform inthickness (i.e., variation in thickness is not more than about 20% fromthe average thickness of that layer), and has an average thickness of atleast about 0.25 μm.

As used in this application, the term “posterior outer hydrogel layer”in reference to a contact lens means a hydrogel layer that includes theposterior surface of the contact lens, is substantially uniform inthickness (i.e., variation in thickness is not more than about 20% fromthe average thickness of that layer), and has an average thickness of atleast about 0.25 μm.

As used in this application, the term “transition layer” in reference toa contact lens means a layer polymeric material that is located betweenthe inner layer (or the lens bulk material) and one of the anterior andposterior outer hydrogel layers. Each transition layer is substantiallyuniform in thickness (i.e., variation in thickness is not more thanabout 20% from the average thickness of that layer).

In this application, the “average thickness” of an anterior or outerhydrogel layer or a transition layer is simply referred to as the“thickness of an anterior outer hydrogel layer”, “thickness of aposterior outer hydrogel layer” or “thickness of a transition layer”, asmeasured with AFM on a cross section of the contact lens in an indicatedstate, e.g., in fully hydrated state or when being fully hydrated (i.e.,in a phosphate buffered solution, pH˜7.3±0.2), or in dry state (i.e.,fully oven-dried).

FIG. 1 schematically illustrates a contact lens of the invention,according to a preferred embodiment. In accordance with this preferredembodiment of the invention, the contact lens 100 has an anteriorsurface (or front curve or convex surface) 101 and an opposite posteriorsurface (or base curve or concave surface) 102 which is rest on thecornea of the eye when worn by a user. The contact lens 100 comprises aninner (or middle) layer (or lens bulk material) 110 and the anterior andposterior outer hydrogel layers 120. The inner layer 110 is the bulkmaterial of the contact lens 100 and has a 3-dimensional shape veryclose to the contact lens 100. The anterior and posterior outer hydrogellayers 120 are substantially uniform in thickness and made of a hydrogelmaterial substantially free of silicone (preferably totally free ofsilicone) having a higher water content relative to that of the innerlayer 110. The anterior and posterior outer hydrogel layers 120 merge atthe peripheral edge 103 of the contact lens 100 and cover completely theinner layer 110.

FIG. 2 schematically illustrates a contact lens of the invention,according to another preferred embodiment. The contact lens 100comprises an inner (or middle) layer (or lens bulk material) 110, theanterior and posterior outer hydrogel layers 120, and two transitionlayers 115. Each of the two transition layers 115 is located between theinner layer 110 and one of the two outer hydrogel layers 120.

As used in this application, the term “equilibrium water content” inreference to a contact lens or a polymeric material means the amount(expressed as percent by weight) of water present in the contact lens orthe polymeric material when being fully hydrated (equilibrated) insaline solution (ca. 0.79 wt % NaCl) and determined at room temperature(as defined above).

As used in this application, the term “crosslinked coating” or “hydrogelcoating” on a contact lens interchangeably is used to describe acrosslinked polymeric material having a three-dimensional network thatcan contain water when fully hydrated. The three-dimensional network ofa crosslinked polymeric material can be formed by crosslinking of two ormore linear or branched polymers through crosslinkages.

As used in this application, the term “polyquaternium-1 uptake” or “PU”in reference to a contact lens means the amount of polyquaternium-1absorbed by the contact lens, as measured according to the proceduredescribed in Example 1.

As used in this application, the term “long-lasting surfacehydrophilicity and wettability” in reference to a contact lens meansthat the contact lens has a water-break-up time (WBUT) of at least 10seconds after 30 cycles of digital rubbing treatment or after simulatedabrasion cycling treatment. WBUT determination, cycle of digital rubbingtreatment, and simulated abrasion cycling treatment of a contact lensare performed according to the procedures described in Example 1.

As used in this application, the term “long-lasting lubricity” inreference to a contact lens means that the contact lens has a frictionrating of about 2.0 or lower after 30 cycles of digital rubbingtreatment or after simulated abrasion cycling treatment. Friction ratingdetermination, cycle of digital rubbing treatment, and simulatedabrasion cycling treatment of a contact lens are performed according tothe procedures described in Example 1.

As used in this application, the term “30 cycles of digital rubbingtreatment” or “n cycles of digital rubbing treatment” means that contactlenses are subjected to 30 or n repetitions of a digital rubbingprocedure which essentially consists of digitally rubbing (wearingdisposable powder-free latex gloves) contact lenses with RENU®multi-purpose lens care solution (or an equivalent, i.e., amulti-purpose lens care solution disclosed in Table I of U.S. Pat. No.5,858,937 for 20 seconds and then rinsing the digitally-rubbed contactlenses with a phosphate-buffered saline for at least 20 seconds. The 30(or n) cycles of digital rubbing treatment can reasonably imitate dailycleaning and disinfecting in a 30-days or n-days lens care regime.

The term “inherently wettable” or “naturally-wettable” in reference to asilicone hydrogel contact lens interchangeably means that the siliconehydrogel contact lens has water-break-up-time (WBUT) of about 10 secondsor more and a water contact angle by captive bubble (WCA_(cb)) of about80 degree or less without being subjected to any surface treatment afterthe silicone hydrogel contact lens is formed by thermally or actinicallypolymerizing (i.e., curing) a silicone hydrogel lens formulation. Inaccordance with the invention, WBUT and WCA_(cb) are measured accordingto the procedures described in Example 1.

“Surface modification” or “surface treatment”, as used herein, meansthat an article has been treated in a surface treatment process (or asurface modification process) prior to or posterior to the formation ofthe article, in which (1) a coating is applied to the surface of thearticle, (2) chemical species are adsorbed onto the surface of thearticle, (3) the chemical nature (e.g., electrostatic charge) ofchemical groups on the surface of the article are altered, or (4) thesurface properties of the article are otherwise modified. Exemplarysurface treatment processes include, but are not limited to, a surfacetreatment by energy (e.g., a plasma, a static electrical charge,irradiation, or other energy source), chemical treatments, the graftingof hydrophilic vinylic monomers or macromers onto the surface of anarticle, mold-transfer coating process disclosed in U.S. Pat. No.6,719,929, the incorporation of wetting agents into a lens formulationfor making contact lenses proposed in U.S. Pat. Nos. 6,367,929 and6,822,016, reinforced mold-transfer coating disclosed in U.S. Pat. No.7,858,000, and a hydrophilic coating composed of covalent attachment orphysical deposition of one or more layers of one or more hydrophilicpolymer onto the surface of a contact lens disclosed in U.S. Pat. Nos.8,147,897 and 8,409,599 and US Pat. Appl. Pub. Nos. 2011/0134387,2012/0026457 and 2013/0118127.

“Post-curing surface treatment”, in reference to a lens bulk material ora contact lens, means a surface treatment process that is performedafter the lens bulk material or the contact lens is formed by curing(i.e., thermally or actinically polymerizing) a lens formulation. A“lens formulation” refers to a polymerizable composition that comprisesall necessary polymerizable components for producing a contact lens or alens bulk material as well known to a person skilled in the art.

An “organic-based solution” refers to a solution which is a homogeneousmixture consisting of an organic-based solvent and one or more solutesdissolved in the organic based solvent. An organic-based coatingsolution refers to an organic-based solution containing at least onepolymeric coating material as a solute in the solution.

An “organic-based solvent” is intended to describe a solvent systemwhich consists of one or more organic solvents and about 40% or less,preferably about 30% or less, more preferably about 20% or less, evenmore preferably about 10% or less, in particular about 5% or less byweight of water relative to the weight of the solvent system.

The invention is generally related to a process for producing weekly- ormonthly-disposable water gradient contact lenses each of which not onlyhas a layered structural configuration providing a unique water gradientfrom inside to outside of the contact lens and a relatively long-lastingwettability/hydrophilicity, but also is digital rubbing resistant andcompatible with lens care solutions including multipurpose lens caresolutions. The layered structural configuration comprises: an innerlayer (i.e., a bulk lens material) having an equilibrium water contentof about 70% by weight or less and an outer surface hydrogel layer whichfully covers the inner layer (or lens bulk material) and has anequilibrium water content being at least 1.2 folds of the equilibriumwater content of the inner layer (or lens bulk material) (preferablybeing at least 80% by weight) and an adequate thickness (from about 0.25μm to about 25 μm) when being fully hydrated.

In accordance with the invention, the anterior and posterior outerhydrogel layers must not only have a relatively-low elastic modulus butalso have an adequate thickness in order to provide a superior wearingcomfort. A relatively-low elastic modulus of the anterior and posteriorouter hydrogel layers (or together as an outer surface hydrogel layer)can ensure the contact lens have an extremely soft surface with highequilibrium water content. But, if the outer surface hydrogel layer istoo thin, it would be susceptible to be totally collapsed onto the lensbulk material by a slight compressing force, losing the advantagesassociated with the water gradient structural feature of a contact lensof the invention. It is believed that for a given low elastic modulusthe wearing comfort provided by a contact lens of the invention wouldincrease with the increase of the thickness of its outer surfacehydrogel layer and then level off after a certain thickness value.

It is discovered that, in order to forming a relatively-thick outersurface hydrogel layer on a contact lens required for having a desiredwearing comfort, it is necessary to form a relatively thick anchor layer(i.e., reactive base coating) of a reactive polymer (e.g., acarboxyl-containing polyanionic polymer) on a contact lens. The thickerthe anchor layer, the thicker the outer surface hydrogel layer. However,the relatively thick anchor layer give rises to higher concentrations ofreactive groups (e.g., carboxyl groups) in the anchor layer and higheruptakes of positively-charged antimicrobials present in lens caresolutions. The past efforts in reducing the uptakes ofpositively-charged antimicrobials by water gradient contact lensesprimarily relied on the reduction of the thickness of the anchor layerand use of a polyanionic material having a higher pKa value. Suchapproaches yield an outer surface hydrogel layer too thin that thedurability and lubricity of the outer surface hydrogel layer is reducedand the wear comfort provided by the resultants contact lenses isdiminished. It is discovered that a water gradient contact lens with athick outer surface hydrogel layer thereon can be produced in a processcomprising a step of heating a contact lens precursor with an anchorlayer of a polyanionic polymer in an aqueous solution comprising atleast one low molecular weight polyaziridine and at least onethermally-crosslinkable hydrophilic polymeric material to form an outersurface hydrogel layer which is covalently attached to the anchor layer,to convert a majority or most negatively-charged groups in the watergradient contact lens into non-charged ester groups through aziridinegroups to minimize or eliminate uptake of a polycationic antimicrobial,and to crosslinked the anchor layer through a polyaziridine as aflexible crosslinker so as to enforce the durability of the outersurface hydrogel layer while having no or minimal adverse impacts on thewettability, hydrophilicity, and lubricity of the outer surface hydrogellayer on the contact lens. The water gradient contact lenses producedaccording to a process of the invention are compatible with multipurposelens care solutions and resistant to digital rubbing and thereforesuitable to be used as weekly- or monthly-disposable contact lenses.Because they have the desired water gradient structural configurationand a relatively-thick, extremely-soft and water-rich hydrogel surfacelayer, they can provide superior wearing comfort.

The invention, in one aspect, provides a process for producing a contactlens, comprising the steps of (a) obtaining a contact lens precursorwhich is a coated contact lens which comprises a lens bulk materialcompletely covered with an anchor layer of a polyanionic polymer whichcomprises at least 60% by mole of repeating units of at least onecarboxyl-containing vinylic monomer; and (b) heating, in the presence ofat least one first polyaziridine which has a number average molecularweight of about 2000 Dalton or less (preferably from 250 Daltons to 1500Daltons, more preferably from 300 Dalton to 1000 Dalton, even morepreferably from 350 Dalton to about 800 Daltons) and at least twoaziridine groups, the contact lens precursor in a first aqueous solutionwhich comprises a thermally-crosslinkable hydrophilic polymeric materialwhich has azetidinium groups and optionally (but preferably) aminogroups, thiol groups, carboxyl groups, or combinations thereof, in thepresence of at least one polyaziridine to and at a temperature fromabout 30° C. to about 140° C. for a period of time sufficient to obtainthe contact lens, wherein the contact lens comprise (i) a crosslinkanchor layer thereon and (2) an outer surface hydrogel layer which iscovalently attached to the crosslinked anchor layer, wherein thecrosslinked anchor layer is obtained by crosslinking the polyanionicpolymer in the anchor layer via crosslinkers derived from said at leastone polyaziridine in coupling reaction between at least one pair ofaziridine and carboxyl groups, wherein the outer surface hydrogel layeris formed by crosslinking the thermally-crosslinked hydrophilicpolymeric material. Preferably, the contact lens has a water-break-uptime of at least 10 seconds (preferably at least 12.5 seconds, morepreferably at least 15 seconds, even more preferably at least 17.5seconds, most preferably at least 20 seconds) or a friction rating ofabout 2.0 or lower (preferably about 1.5 or lower, more preferably about1.0 or lower, even more preferably about 0.5 or lower) after 30 cyclesof digital rubbing treatment or after simulated abrasion cyclingtreatment and a polyquaternium-1 uptake (“PU_(pz)”) of about 0.6 μg/lensor less (preferably about 0.5 μg/lens or less, more preferably about 0.4μg/lens or less, even more preferably about 0.3 μg/lens or less, mostpreferably about 0.2 μg/lens or less).

A contact lens precursor with an anchor layer of a polyanionic polymerthereon can be obtained according to any methods known to a personskilled in the art. For instance, a contact lens precursor with ananchor layer of a polyanionic polymer thereon can be obtained either bycontacting a preformed contact lens with a solution of a polyanionicpolymer at a pH of from about 1.0 to about 3.0 for a time periodsufficient long to form the anchor layer of the polyanionic polymer witha desired thickness (as illustrated in more detail below) or by graftinga polyanionic polymer onto the surface of a preformed contact lens,according to any graft polymerization techniques known to a personskilled in the art (as illustrated in more detail below).

In accordance with the invention, a preformed contact lens can be anycontact lens which has not been subjected to any surface treatment afterbeing produced according to any lens manufacturing processes, anycontact lens which has been plasma treated, or any commercial contactlens, so long as it does not have a water gradient structuralconfiguration. A person skilled in the art knows very well how to makepreformed contact lenses. For example, preformed contact lenses can beproduced in a conventional “spin-casting mold,” as described for examplein U.S. Pat. No. 3,408,429, or by the full cast-molding process in astatic form, as described in U.S. Pat. Nos. 4,347,198; 5,508,317;5,583,463; 5,789,464; and 5,849,810, or by lathe cutting of polymericmaterial buttons as used in making customized contact lenses. Incast-molding, a lens formulation typically is dispensed into molds andcured (i.e., polymerized and/or crosslinked) in molds for making contactlenses.

Lens molds for making contact lenses are well known to a person skilledin the art and, for example, are employed in cast molding or spincasting. For example, a mold (for cast molding) generally comprises atleast two mold sections (or portions) or mold halves, i.e. first andsecond mold halves. The first mold half defines a first molding (oroptical) surface and the second mold half defines a second molding (oroptical) surface. The first and second mold halves are configured toreceive each other such that a lens forming cavity is formed between thefirst molding surface and the second molding surface. The moldingsurface of a mold half is the cavity-forming surface of the mold and indirect contact with lens-forming material.

Methods of manufacturing mold sections for cast-molding a contact lensare generally well known to those of ordinary skill in the art. Theprocess of the present invention is not limited to any particular methodof forming a mold. In fact, any method of forming a mold can be used inthe present invention. The first and second mold halves can be formedthrough various techniques, such as injection molding or lathing.Examples of suitable processes for forming the mold halves are disclosedin U.S. Pat. Nos. 4,444,711; 4,460,534; 5,843,346; and 5,894,002.

Virtually all materials known in the art for making molds can be used tomake molds for making contact lenses. For example, polymeric materials,such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade8007-S10 (clear amorphous copolymer of ethylene and norbornene, fromTicona GmbH of Frankfurt, Germany and Summit, N.J.), or the like can beused. Other materials that allow UV light transmission could be used,such as quartz glass and sapphire.

In a preferred embodiment, reusable molds are used and the lens-formingcomposition is cured actinically under a spatial limitation of actinicradiation to form a contact lens. Examples of preferred reusable moldsare those disclosed in U.S. Pat. Nos. 6,627,124, 6,800,225, 7,384,590,and 7,387,759. Reusable molds can be made of quartz, glass, sapphire,CaF₂, a cyclic olefin copolymer (e.g., Topas® COC grade 8007-S10 (clearamorphous copolymer of ethylene and norbornene) from Ticona GmbH ofFrankfurt, Germany and Summit, N.J., Zeonex® and Zeonor® from ZeonChemicals LP, Louisville, Ky.), polymethylmethacrylate (PMMA),polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from G.E.Plastics, PrimoSpire®, etc.

In accordance with the invention, the polymerizable composition can beintroduced (dispensed) into a cavity formed by a mold according to anyknown methods.

After the polymerizable composition is dispensed into the mold, it ispolymerized to produce a contact lens. Crosslinking may be initiatedthermally or actinically, preferably by exposing the lens-formingcomposition in the mold to a spatial limitation of actinic radiation tocrosslink the polymerizable components in the polymerizable composition.

Opening of the mold so that the molded article can be removed from themold may take place in a manner known per se.

The molded contact lens can be subject to lens extraction to removeunpolymerized polymerizable components. The extraction solvent can beany solvent known to a person skilled in the art. Examples of suitableextraction solvent are those described below.

In a preferred embodiment, a preformed contact lens is a hard contactlens comprising a hard plastic material as lens bulk material.Preferably, the hard plastic material is a crosslinkedpolymethylacrylate. A person skilled in the art knows well how to make ahard plastic material, including a crosslinked polymethylmethacrylate.

In another preferred embodiment, a preformed contact lens is a rigid gaspermeable contact lens. A person skilled in the art knows how to make arigid gas permeable contact lens.

In another preferred embodiment, a preformed contact lens is a hybridcontact lens having a central optical zone (i.e., a central circularportion) made of a rigid gas permeable lens material and a peripheralzone (i.e., an annular portion) surrounding the central optical zone(i.e., the central circular portion) and made of a hydrogel material.

In another preferred embodiment, a preformed contact lens is a softsilicone contact lens comprising, as lens bulk material, a crosslinkedsilicone material. Useful crosslinked silicone materials include,without limitation, crosslinked polysiloxanes obtained by crosslinkingsilicone composition according to any know method, silicone elastomers,silicone rubbers, and the likes. Silicone contact lenses can be preparedby any kind of conventional techniques (for example, the lathe cutmanufacturing method, the spin cast manufacturing method, the castmolding manufacturing method, etc.) well-known to a person skilled inthe art.

In another preferred embodiment, a preformed contact lens is anon-silicone hydrogel contact lens (or so-called a conventional hydrogelcontact lens). Preformed non-silicone hydrogel contact lenses can be anycommercially-available non-silicone hydrogel contact lenses or can beproduced according to any known methods. For example, for production ofpreformed non-silicone hydrogel contact lenses, a non-silicone hydrogellens formulation for cast-molding or spin-cast molding or for makingrods used in lathe-cutting of contact lenses typically is: either (1) amonomer mixture comprising (a) at least one hydrophilic vinylic monomer(e.g., hydroxyethyl methacrylate, glycerol methacrylate,N-vinylpyrrolidone, or combinations thereof) and (b) at least onecomponent selected from the group consisting of a crosslinking agent, ahydrophobic vinylic monomer, a lubricating agent (or so-called internalwetting agents incorporated in a lens formulation), a free-radicalinitiator (photoinitiator or thermal initiator), a UV-absorbing vinylicmonomer, a high-energy-violet-light (“HEVL”) absorbing vinylic monomer,a visibility tinting agent (e.g., reactive dyes, polymerizable dyes,pigments, or mixtures thereof), antimicrobial agents (e.g., preferablysilver nanoparticles), a bioactive agent, and combinations thereof; or(2) an aqueous solution comprising one or more water-soluble prepolymersand at least one component selected from the group consisting ofhydrophilic vinylic monomer, a crosslinking agent, a hydrophobic vinylicmonomer, a lubricating agent (or so-called internal wetting agentsincorporated in a lens formulation), a free-radical initiator(photoinitiator or thermal initiator), a UV-absorbing vinylic monomer, aHEVL absorbing vinylic monomer, a visibility tinting agent (e.g.,reactive dyes, polymerizable dyes, pigments, or mixtures thereof),antimicrobial agents (e.g., preferably silver nanoparticles), abioactive agent, and combinations thereof. Resultant preformed hydrogelcontact lenses then can be subjected to extraction with an extractionsolvent to remove unpolymerized components from the resultant lenses andto hydration process, as known by a person skilled in the art. It isunderstood that a lubricating agent present in a hydrogel lensformulation can improve the lubricity of preformed hydrogel contactlenses compared to the lubricity of control preformed hydrogel contactlenses obtained from a control hydrogel lens formulation without thelubricating agent.

Examples of water-soluble prepolymers include without limitation: awater-soluble crosslinkable poly(vinyl alcohol) prepolymer described inU.S. Pat. Nos. 5,583,163 and 6,303,687; a water-soluble vinylgroup-terminated polyurethane prepolymer described in U.S. Pat. No.6,995,192; derivatives of a polyvinyl alcohol, polyethyleneimine orpolyvinylamine, which are disclosed in U.S. Pat. No. 5,849,841; awater-soluble crosslinkable polyurea prepolymer described in U.S. Pat.Nos. 6,479,587 and 7,977,430; crosslinkable polyacrylamide;crosslinkable statistical copolymers of vinyl lactam, MMA and acomonomer, which are disclosed in U.S. Pat. No. 5,712,356; crosslinkablecopolymers of vinyl lactam, vinyl acetate and vinyl alcohol, which aredisclosed in U.S. Pat. No. 5,665,840; polyether-polyester copolymerswith crosslinkable side chains which are disclosed in U.S. Pat. No.6,492,478; branched polyalkylene glycol-urethane prepolymers disclosedin U.S. Pat. No. 6,165,408; polyalkylene glycol-tetra(meth)acrylateprepolymers disclosed in U.S. Pat. No. 6,221,303; crosslinkablepolyallylamine gluconolactone prepolymers disclosed in U.S. Pat. No.6,472,489.

Numerous non-silicone hydrogel lens formulations have been described innumerous patents and patent applications published by the filing date ofthis application and have been used in producing commercial non-siliconehydrogel contact lenses. Examples of commercial non-silicone hydrogelcontact lenses include, without limitation, alfafilcon A, acofilcon A,deltafilcon A, etafilcon A, focofilcon A, helfilcon A, helfilcon B,hilafilcon B, hioxifilcon A, hioxifilcon B, hioxifilcon D, methafilconA, methafilcon B, nelfilcon A, nesofilcon A, ocufilcon A, ocufilcon B,ocufilcon C, ocufilcon D, omafilcon A, phemfilcon A, polymacon,samfilcon A, telfilcon A, tetrafilcon A, and vifilcon A.

In a preferred embodiment, the preformed contact lens is a non-siliconehydrogel contact lens comprising a non-silicone hydrogel bulk materialwhich comprises at least 50% by mole of repeating units of at least onehydroxyl-containing vinylic monomer, preferably selected from the groupconsisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate,3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate,3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl(meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl(meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide,N-tris(hydroxymethyl)methyl (meth)acrylamide, vinyl alcohol, allylalcohol, and combinations thereof, more preferably selected from thegroup consisting of hydroxyethyl (meth)acrylate, glycerol(meth)acrylate, and vinyl alcohol. The mole percentages of repeatingunits can be calculated based on a non-silicone hydrogel lensformulation for making the non-silicone hydrogel contact lens.Alternatively, the preformed contact lens is a commercial non-siliconehydrogel contact lens (any one listed above).

In another preferred embodiment, a preformed contact lens is a siliconehydrogel contact lens, preferably a naturally-wettable silicone hydrogelcontact lens.

Preformed silicone hydrogel contact lenses can be anycommercially-available silicone hydrogel contact lenses or can beproduced according to any known methods from a SiHy lens formulation.For example, for production of preformed silicone hydrogel (SiHy)contact lenses, a SiHy lens formulation for cast-molding or spin-castmolding or for making SiHy rods used in lathe-cutting of contact lensesgenerally comprises at least one components selected from the groupconsisting of a silicone-containing vinylic monomer, asilicone-containing vinylic crosslinker, a silicone-containingprepolymer, a hydrophilic vinylic monomer, a hydrophobic vinylicmonomer, a non-silicone vinylic crosslinker, a free-radical initiator(photoinitiator or thermal initiator), a silicone-containing prepolymer,and combination thereof, as well known to a person skilled in the art.Resultant preformed SiHy contact lenses then can be subjected toextraction with an extraction solvent to remove unpolymerized componentsfrom the resultant lenses and to hydration process, as known by a personskilled in the art. In addition, a preformed SiHy contact lens can be acolored contact lens (i.e., a SiHy contact lens having at least onecolored patterns printed thereon as well known to a person skilled inthe art).

In accordance with the invention, a silicone-containing vinylic monomercan be any silicone-containing vinylic monomer known to a person skilledin the art. Examples of preferred silicone-containing vinylic monomersinclude without limitation vinylic monomers each having abis(trialkylsilyloxy)alkylsilyl group or a tris(trialkylsilyloxy)silylgroup, polysiloxane vinylic monomers, polycarbosiloxane vinylic monomer,3-methacryloxy propylpentamethyldisiloxane, t-butyldimethyl-siloxyethylvinyl carbonate, trimethylsilylethyl vinyl carbonate, andtrimethylsilylmethyl vinyl carbonate, and combinations thereof.

Examples of preferred vinylic monomers each having abis(trialkylsilyloxy)alkylsilyl group or a tris(trialkylsilyloxy)silylgroup include without limitation tris(trimethylsilyloxy)silylpropyl(meth)acrylate,[3-(meth)acryloxy-2-hydroxypropyloxy]propylbis(trimethylsiloxy)methylsilane,[3-(meth)acryloxy-2-hydroxypropyloxy]propylbis(trimethylsiloxy)butylsilane,3-(meth)acryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane,3-(meth)acryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide,N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methysilyl)propyloxy)propyl)-2-methyl(meth)acrylamide,N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)(meth)acrylamide,N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide,N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)(meth)acrylamide,N-[tris(dimethylpropylsiloxy)silylpropyl]-(meth)acrylamide,N-[tris(dimethylphenylsiloxy)silylpropyl](meth)acrylamide,N-[tris(dimethylethylsiloxy)silylpropyl] (meth)acrylamide,N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide,N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl](meth)acrylamide,N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methyl(meth)acrylamide,N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl](meth)acrylamide,N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide,N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl](meth)acrylamide,N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methyl(meth)acrylamide,N-2-(meth)acryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)propylvinyl carbonate,3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane,3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate,3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate, those disclosed inU.S. Pat. Nos. 9,097,840, 9,103,965 and 9,475,827, and mixtures thereof.The above preferred silicone-containing vinylic monomers can be obtainedfrom commercial suppliers or can be prepared according to proceduresdescribed in U.S. Pat. Nos. 7,214,809, 8,475,529, 8,658,748, 9,097,840,9,103,965, and 9,475,827.

Examples of preferred polysiloxane vinylic monomers include withoutlimitation mono-(meth)acryloyl-terminated, monoalkyl-terminatedpolysiloxanes of formula (I) include without limitationα-(meth)acryloxypropyl terminated ω-butyl (or ω-methyl) terminatedpolydimethylsiloxane, α-(meth)acryloxy-2-hydroxypropyloxypropylterminated ω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-(2-hydroxyl-methacryloxypropyloxypropyl)-ω-butyl-decamethylpentasiloxane,α-[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl]-terminated ω-butyl(or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxy-propyloxy-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxyisopropyloxy-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxybutyloxy-2-hydroxypropyloxypropyl]-terminated ω-butyl(or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloxy-butylamino-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-(meth)acryloxy(polyethylenoxy)-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl]-terminated ω-butyl(or ω-methyl) terminated polydimethylsiloxane,α-[(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl]-terminated ω-butyl(or ω-methyl) terminated polydimethylsiloxane,α-[(meth)acryloxy-2-hydroxypropyl-aminopropyl]-terminated ω-butyl (orω-methyl) terminated polydimethylsiloxane,α-[(meth)acryloxy-2-hydroxypropyloxy-(polyethylenoxy)propyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-(meth)acryloylamidopropyloxypropyl terminated ω-butyl (or ω-methyl)terminated polydimethylsiloxane,α-N-methyl-(meth)acryloylamidopropyloxypropyl terminated ω-butyl (orω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acrylamidoethoxy-2-hydroxypropyloxy-propyl]-terminatedω-butyl (or ω-methyl) polydimethylsiloxane,α-[3-(meth)acrylamidopropyloxy-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acrylamidoisopropyloxy-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acrylamidobutyloxy-2-hydroxypropyloxypropyl]-terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,α-[3-(meth)acryloylamido-2-hydroxypropyloxypropyl] terminated ω-butyl(or ω-methyl) polydimethylsiloxane,α-[3-[N-methyl-(meth)acryloylamido]-2-hydroxypropyloxypropyl] terminatedω-butyl (or ω-methyl) terminated polydimethylsiloxane,N-methyl-N′-(propyltetra(dimethylsiloxy)dimethylbutylsilane)(meth)acrylamide,N-(2,3-dihydroxypropane)-N′-(propyltetra(dimethylsiloxy)dimethylbutylsilane)(meth)acrylamide,(meth)acryloylamidopropyltetra(dimethylsiloxy)dimethylbutylsilane,monovinyl carbonate-terminated mono-alkyl-terminatedpolydimethylsiloxanes, monovinyl carbamate-terminatedmono-alkyl-terminated polydimethylsiloxane, those disclosed in U.S. Pat.Nos. 9,097,840 and 9,103,965, and mixtures thereof. The above preferredpolysiloxanes vinylic monomers can be obtained from commercial suppliers(e.g., Shin-Etsu, Gelest, etc.) or prepared according to proceduresdescribed in patents, e.g., U.S. Pat. Nos. 6,867,245, 8,415,405,8,475,529, 8,614,261, and 9,217,813, or by reacting a hydroxyalkyl(meth)acrylate or (meth)acrylamide or a (meth)acryloxypolyethyleneglycol with a mono-epoxypropyloxypropyl-terminated polydimethylsiloxane,by reacting glycidyl (meth)acrylate with a mono-carbinol-terminatedpolydimethylsiloxane, a mono-aminopropyl-terminatedpolydimethylsiloxane, or a mono-ethylaminopropyl-terminatedpolydimethylsiloxane, or by reacting isocyanatoethyl (meth)acrylate witha mono-carbinol-terminated polydimethylsiloxane according to couplingreactions well known to a person skilled in the art.

Any polycarbosiloxane vinylic monomers can be used in the invention.Examples of preferred polycarbosiloxane vinylic monomers include withoutlimitation those disclosed in U.S. Pat. Nos. 7,915,323 and 8,420,711 andin U.S. Pat. Appl. Pub. Nos. 2012/244088A1 and 2012/245249A1.

Any suitable silicone-containing vinylic crosslinkers can be used in theinvention. Examples of preferred silicone-containing vinyliccrosslinkers include without limitation polysiloxane vinyliccrosslinkers, polycarbosiloxane vinylic crosslinkers, and combinationsthereof.

Any suitable polysiloxane vinylic crosslinkers can be used in theinvention. Examples of preferred polysiloxane vinylic crosslinkers aredi-(meth)acryloyl-terminated polydimethylsiloxanes; di-vinylcarbonate-terminated polydimethylsiloxanes; di-vinylcarbamate-terminated polydimethylsiloxane;N,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-alpha,omega-bis-3-aminopropyl-polydimethylsiloxane;polysiloxane-containing macromer selected from the group consisting ofMacromers A to D described in U.S. Pat. No. 5,760,100;polysiloxane-containing macromers disclosed in U.S. Pat. Nos. 4,136,250,4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147,4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712,4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586,4,954,587, 5,010,141, 5,034,461, 5,070,170, 5,079,319, 5,039,761,5,346,946, 5,358,995, 5,387,632, 5,416,132, 5,451,617, 5,486,579,5,962,548, 5,981,675, 6,039,913, and 6,762,264; polysiloxane-containingmacromers disclosed in U.S. Pat. Nos. 4,259,467, 4,260,725, and4,261,875.

Examples of preferred di-(meth)acryloyloxy-terminated polysiloxanevinylic crosslinkers includes without limitation the reaction productsof glycidyl methacrylate with di-amino-terminated polydimethylsiloxanes;the reaction products of glycidyl methacrylate withdi-hydroxyl-terminated polydimethylsiloxanes; the reaction products ofisocyantoethyl (meth)acrylate with di-hydroxyl-terminatedpolydimethylsiloxanes; di-(meth)acryloyloxy-terminated polysiloxanevinylic crosslinkers each having hydrophilized siloxane units eachhaving one methyl substituent and one monovalent C₄-C₄₀ organic radicalsubstituent having 2 to 6 hydroxyl groups as disclosed in U.S. patentSer. No. 10/081,697; chain-extended polysiloxabe vinylic crosslinkersdisclosed in US201008843A1 and US20120088844A1; chain-extendedpolysiloxane vinylic crosslinkers described in U.S. Pat. Nos. 5,034,461,5,416,132, 5,449,729, 5,760,100, 7,423,074, and 8,529,057;chain-extended polysiloxane vinylic crosslinkers described in U.S. Pat.App. Pub. No. 2018-0100053; chain-extended polysiloxane vinyliccrosslinkers described in U.S. Pat. App. Pub. No. 2018-0100038;chain-extended polysiloxane vinylic crosslinkers described in U.S. Pat.No. 8,993,651; α,ω-bis[3-(meth)acrylamidopropyl]-terminatedpolydimethylsiloxane, α,ω-bis[3-(meth)acryloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxyethoxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxypropyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxy-isopropyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxybutyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamidoethoxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamidopropyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamidoisopropyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamidobutyloxy-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxyethylamino-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxypropylamino-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acryloxybutylamino-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acrylamidoethylamino-2-hydroxypropyloxy-propyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamidopropylamino-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[3-(meth)acrylamide-butylamino-2-hydroxypropyloxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acryloxy-2-hydroxypropyloxy-ethoxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acryloxy-2-hydroxypropyl-N-ethylaminopropyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acryloxy-2-hydroxypropyl-aminopropyl]-polydimethylsiloxane,α,ω-bis[(meth)acryloxy-2-hydroxypropyloxy-(polyethylenoxy)propyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acryloxyethylamino-carbonyloxy-ethoxypropyl]-terminatedpolydimethylsiloxane,α,ω-bis[(meth)acryloxyethylamino-carbonyloxy-(polyethylenoxy)propyl]-terminatedpolydimethylsiloxane.

Any polycarbosiloxane vinylic crosslinkers can be used in the invention.Examples of preferred polycarbosiloxane vinylic crosslinkers includewithout limitation those disclosed in U.S. Pat. Nos. 7,915,323 and8,420,711 and in U.S. Pat. Appl. Pub. Nos. 2012/244088A1 and2012/245249A1.

Any hydrophilic vinylic monomers can be used in the invention. Examplesof preferred hydrophilic vinylic monomers are alkyl (meth)acrylamides(as described below), hydroxyl-containing acrylic monomers (as describedbelow), amino-containing acrylic monomers (as described below),carboxyl-containing acrylic monomers (as described below), N-vinyl amidemonomers (as described below), methylene-containing pyrrolidone monomers(i.e., pyrrolidone derivatives each having a methylene group connectedto the pyrrolidone ring at 3- or 5-position) (as described below),acrylic monomers having a C₁-C₄ alkoxyethoxy group (as described below),vinyl ether monomers (as described below), allyl ether monomers (asdescribed below), phosphorylcholine-containing vinylic monomers (asdescribed below), N-2-hydroxyethyl vinyl carbamate,N-carboxyvinyl-β-alanine (VINAL), N-carboxyvinyl-α-alanine, andcombinations thereof.

Examples of alkyl (meth)acrylamides includes without limitation(meth)acrylamide, N,N-dimethyl (meth)acrylamide, N-ethyl(meth)acrylamide, N,N-diethyl (meth)acrylamide, N-propyl(meth)acrylamide, N-isopropyl (meth)acrylamide, N-3-methoxypropyl(meth)acrylamide, and combinations thereof.

Examples of hydroxyl-containing acrylic monomers include withoutlimitation N-2-hydroxylethyl (meth)acrylamide, N,N-bis(hydroxyethyl)(meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl(meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide,N-tris(hydroxymethyl)methyl (meth)acrylamide, 2-hydroxyethyl(meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl(meth)acrylate, glycerol methacrylate (GMA), di(ethylene glycol)(meth)acrylate, tri(ethylene glycol) (meth)acrylate, tetra(ethyleneglycol) (meth)acrylate, poly(ethylene glycol) (meth)acrylate having anumber average molecular weight of up to 1500, poly(ethyleneglycol)ethyl (meth)acrylamide having a number average molecular weightof up to 1500, and combinations thereof.

Examples of amino-containing acrylic monomers include without limitationN-2-aminoethyl (meth)acrylamide, N-2-methylaminoethyl (meth)acrylamide,N-2-ethylaminoethyl (meth)acrylamide, N-2-dimethylaminoethyl(meth)acrylamide, N-3-aminopropyl (meth)acrylamide,N-3-methylaminopropyl (meth)acrylamide, N-3-dimethylaminopropyl(meth)acrylamide, 2-aminoethyl (meth)acrylate, 2-methylaminoethyl(meth)acrylate, 2-ethylaminoethyl (meth)acrylate, 3-aminopropyl(meth)acrylate, 3-methylaminopropyl (meth)acrylate, 3-ethylaminopropyl(meth)acrylate, 3-amino-2-hydroxypropyl (meth)acrylate,trimethylammonium 2-hydroxy propyl (meth)acrylate hydrochloride,dimethylaminoethyl (meth)acrylate, and combinations thereof.

Examples of carboxyl-containing acrylic monomers include withoutlimitation 2-(meth)acrylamidoglycolic acid, (meth)acrylic acid,ethylacrylic acid, and combinations thereof.

Examples of preferred N-vinyl amide monomers include without limitationN-vinylpyrrolidone (aka, N-vinyl-2-pyrrolidone),N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-4-methyl-2-pyrrolidone,N-vinyl-5-methyl-2-pyrrolidone, N-vinyl-6-methyl-2-pyrrolidone,N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone,N-vinyl-5,5-dimethyl-2-pyrrolidone,N-vinyl-3,3,5-trimethyl-2-pyrrolidone, N-vinyl piperidone (aka,N-vinyl-2-piperidone), N-vinyl-3-methyl-2-piperidone,N-vinyl-4-methyl-2-piperidone, N-vinyl-5-methyl-2-piperidone,N-vinyl-6-methyl-2-piperidone, N-vinyl-6-ethyl-2-piperidone,N-vinyl-3,5-dimethyl-2-pipendone, N-vinyl-4,4-dimethyl-2-piperidone,N-vinyl caprolactam (aka, N-vinyl-2-caprolactam),N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-caprolactam,N-vinyl-7-methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam,N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactam,N-vinyl-3,5,7-trimethyl-2-caprolactam, N-vinyl-N-methyl acetamide,N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, and mixturesthereof. Preferably, the N-vinyl amide monomer is N-vinylpyrrolidone,N-vinyl-N-methyl acetamide, or combinations thereof.

Examples of preferred methylene-containing (═CH₂) pyrrolidone monomersinclude without limitations 1-methyl-3-methylene-2-pyrrolidone,1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone,5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone,1-n-propyl-5-methylene-2-pyrrolidone,1-isopropyl-3-methylene-2-pyrrolidone,1-isopropyl-5-methylene-2-pyrrolidone,1-n-butyl-3-methylene-2-pyrrolidone,1-tert-butyl-3-methylene-2-pyrrolidone, and combinations thereof.

Examples of preferred acrylic monomers having a C₁-C₄ alkoxyethoxy groupinclude without limitation ethylene glycol methyl ether (meth)acrylate,di(ethylene glycol) methyl ether (meth)acrylate, tri(ethylene glycol)methyl ether (meth)acrylate, tetra(ethylene glycol) methyl ether(meth)acrylate, C₁-C₄-alkoxy poly(ethylene glycol) (meth)acrylate havinga weight average molecular weight of up to 1500, methoxy-poly(ethyleneglycol)ethyl (meth)acrylamide having a number average molecular weightof up to 1500, and combinations thereof.

Examples of preferred vinyl ether monomers include without limitationethylene glycol monovinyl ether, di(ethylene glycol) monovinyl ether,tri(ethylene glycol) monovinyl ether, tetra(ethylene glycol) monovinylether, poly(ethylene glycol) monovinyl ether, ethylene glycol methylvinyl ether, di(ethylene glycol) methyl vinyl ether, tri(ethyleneglycol) methyl vinyl ether, tetra(ethylene glycol) methyl vinyl ether,poly(ethylene glycol) methyl vinyl ether, and combinations thereof.

Examples of preferred allyl ether monomers include without limitationallyl alcohol, ethylene glycol monoallyl ether, di(ethylene glycol)monoallyl ether, tri(ethylene glycol) monoallyl ether, tetra(ethyleneglycol) monoallyl ether, poly(ethylene glycol) monoallyl ether, ethyleneglycol methyl allyl ether, di(ethylene glycol) methyl allyl ether,tri(ethylene glycol) methyl allyl ether, tetra(ethylene glycol) methylallyl ether, poly(ethylene glycol) methyl allyl ether, and combinationsthereof.

Examples of preferred phosphorylcholine-containing vinylic monomersinclude without limitation (meth)acryloyloxyethyl phosphorylcholine(aka, MPC, or2-((meth)acryloyloxy)ethyl-2′-(trimethylammonio)ethylphosphate),(meth)acryloyloxypropyl phosphorylcholine (aka,3-((meth)acryloyloxy)propyl-2′-(trimethylammonio)ethylphosphate),4-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate,2-[(meth)acryloylamino]ethyl-2′-(trimethylammonio)-ethylphosphate,3-[(meth)acryloylamino]propyl-2′-(trimethylammonio)ethylphosphate,4-[(meth)acryloylamino]butyl-2′-(trimethylammonio)ethylphosphate,5-((meth)acryloyloxy)pentyl-2′-(trimethylammonio)ethyl phosphate,6-((meth)acryloyloxy)hexyl-2′-(trimethylammonio)-ethylphosphate,2-((meth)acryloyloxy)ethyl-2′-(triethylammonio)ethylphosphate,2-((meth)acryloyloxy)ethyl-2′-(tripropylammonio)ethylphosphate,2-((meth)acryloyloxy)ethyl-2′-(tributylammonio)ethyl phosphate,2-((meth)acryloyloxy)propyl-2′-(trimethylammonio)-ethylphosphate,2-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate,2-((meth)acryloyloxy)pentyl-2′-(trimethylammonio)ethylphosphate,2-((meth)acryloyloxy)hexyl-2′-(trimethylammonio)ethyl phosphate,2-(vinyloxy)ethyl-2′-(trimethylammonio)ethylphosphate,2-(allyloxy)ethyl-2′-(trimethylammonio)ethylphosphate,2-(vinyloxycarbonyl)ethyl-2′-(trimethylammonio)ethyl phosphate,2-(allyloxycarbonyl)ethyl-2′-(trimethylammonio)-ethylphosphate,2-(vinylcarbonylamino)ethyl-2′-(trimethylammonio)ethylphosphate,2-(allyloxycarbonylamino)ethyl-2′-(trimethylammonio)ethyl phosphate,2-(butenoyloxy)ethyl-2′-(trimethylammonio)ethylphosphate, andcombinations thereof.

In accordance with the invention, any hydrophobic vinylic monomers canbe in this invention. Examples of preferred hydrophobic vinylic monomersinclude methyl (meth)acrylate, ethyl (meth)acrylate, propyl(meth)acrylate, isopropyl (meth)acrylate, cyclohexyl (meth)acrylate,2-ethylhexyl (meth)acrylate, vinyl acetate, vinyl propionate, vinylbutyrate, vinyl valerate, styrene, chloroprene, vinyl chloride,vinylidene chloride, (meth)acrylonitrile, 1-butene, butadiene, vinyltoluene, vinyl ethyl ether,perfluorohexylethyl-thio-carbonyl-aminoethyl-methacrylate, isobornyl(meth)acrylate, trifluoroethyl (meth)acrylate, hexafluoro-isopropyl(meth)acrylate, hexafluorobutyl (meth)acrylate, and combinationsthereof.

In accordance with the invention, any non-silicone vinylic crosslinkerscan be in this invention. Examples of preferred non-silicone vinyliccross-linking agents include without limitation ethyleneglycoldi-(meth)acrylate, diethyleneglycol di-(meth)acrylate, triethyleneglycoldi-(meth)acrylate, tetraethyleneglycol di-(meth)acrylate, glyceroldi-(meth)acrylate, 1,3-propanediol di-(meth)acrylate, 1,3-butanedioldi-(meth)acrylate, 1,4-butanediol di-(meth)acrylate, glycerol1,3-diglycerolate di-(meth)acrylate,ethylenebis[oxy(2-hydroxypropane-1,3-diyl)] di-(meth)acrylate,bis[2-(meth)acryloxyethyl] phosphate, trimethylolpropanedi-(meth)acrylate, and 3,4-bis[(meth)acryloyl]tetrahydrofuran,diacrylamide, dimethacrylamide, N,N-di(meth)acryloyl-N-methylamine,N,N-di(meth)acryloyl-N-ethylamine, N,N′-methylene bis(meth)acrylamide,N,N′-ethylene bis(meth)acrylamide, N,N′-dihydroxyethylenebis(meth)acrylamide, N,N′-propylene bis(meth)acrylamide,N,N′-2-hydroxypropylene bis(meth)acrylamide, N,N′-2,3-dihydroxybutylenebis(meth)acrylamide, 1,3-bis(meth)acrylamidepropane-2-yl dihydrogenphosphate, piperazine diacrylamide, tetraethyleneglycol divinyl ether,triethyleneglycol divinyl ether, diethyleneglycol divinyl ether,ethyleneglycol divinyl ether, triallyl isocyanurate, triallyl cyanurate,trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate,bisphenol A dimethacrylate, allylmethacrylate, allylacrylate,N-allyl-methacrylamide, N-allyl-acrylamide, and combinations thereof. Apreferred non-silicone vinylic cross-linking agent istetra(ethyleneglycol) di-(meth)acrylate, tri(ethyleneglycol)di-(meth)acrylate, ethyleneglycol di-(meth)acrylate, di(ethyleneglycol)di-(meth)acrylate, tetraethyleneglycol divinyl ether, triethyleneglycoldivinyl ether, diethyleneglycol divinyl ether, ethyleneglycol divinylether, triallyl isocyanurate, triallyl cyanurate, and combinationsthereof.

Any thermal polymerization initiators can be used in the invention.Suitable thermal polymerization initiators are known to the skilledartisan and comprise, for example peroxides, hydroperoxides,azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates, ormixtures thereof. Examples of preferred thermal polymerizationinitiators include without limitation benzoyl peroxide, t-butylperoxide, t-amyl peroxybenzoate, 2,2-bis(tert-butylperoxy)butane,1,1-bis(tert-butylperoxy)cyclohexane,2,5-Bis(tert-butylperoxy)-2,5-dimethylhexane,2,5-bis(tert-butylperoxy)-2,5-dimethyl-3-hexyne,bis(1-(tert-butylperoxy)-1-methylethyl)benzene,1,1-bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane,di-t-butyl-diperoxyphthalate, t-butyl hydro-peroxide, t-butylperacetate, t-butyl peroxybenzoate, t-butylperoxy isopropyl carbonate,acetyl peroxide, lauroyl peroxide, decanoyl peroxide, dicetylperoxydicarbonate, di(4-t-butylcydohexyl)peroxy dicarbonate (Perkadox16S), di(2-ethylhexyl)peroxy dicarbonate, t-butylperoxy pivalate(Lupersol 11); t-butylperoxy-2-ethylhexanoate (Trigonox 21-C50),2,4-pentanedione peroxide, dicumyl peroxide, peracetic acid, potassiumpersulfate, sodium persulfate, ammonium persulfate,2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) (VAZO 33),2,2′-Azobis[2-(2-imidazolin-2-yl)propane]dihydrochlorde (VAZO 44),2,2′-azobis(2-amidinopropane) dihydrochloride (VAZO 50),2,2′-azobis(2,4-dimethylvaleronitrile) (VAZO 52),2,2′-azobis(isobutyronitrile) (VAZO 64 or AIBN),2,2′-azobis-2-methylbutyronitrile (VAZO 67),1,1-azobis(1-cyclohexanecarbonitrile) (VAZO 88);2,2′-azobis(2-cyclopropylpropionitrile), 2,2′-azobis(methylisobutyrate),4,4′-Azobis(4-cyanovaleric acid), and combinations thereof. Preferably,the thermal initiator is 2,2′-azobis(isobutyronitrile) (AIBN or VAZO64).

Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone,a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and Darocurand Irgacur types, preferably Darocur 1173) and Darocur 2959),Germanium-based Norrish Type I photoinitiators (e.g., those described inU.S. Pat. No. 7,605,190, herein incorporated by reference in itsentirety). Examples of benzoylphosphine initiators include2,4,6-trimethylbenzoyldiphenylophosphine oxide;bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; andbis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactivephotoinitiators which can be incorporated, for example, into a macromeror can be used as a special monomer are also suitable. Examples ofreactive photoinitiators are those disclosed in EP 632 329, hereinincorporated by reference in its entirety.

Any silicone-containing prepolymers comprising hydrophilic segments andhydrophobic segments can be used in the invention. Examples of suchsilicone-containing prepolymers include those described in U.S. Pat.Nos. 6,039,913, 7,091,283, 7,268,189, 7,238,750, 7,521,519, 8,383,744,and 8,642,712; and US Pat. Appl. Pub. Nos. 2008/0015315A1,2008/0143958A1, 2008/0143003A1, 2008/0234457A1, and 2008/0231798A1.

A SiHy contact lens formulation can also comprise other necessarycomponents known to a person skilled in the art, such as, for example, aUV-absorbing vinylic monomer, a HEVL-absorbing vinylic monomer, avisibility tinting agent (e.g., reactive dyes, polymerizable dyes,pigments, or mixtures thereof, as well known to a person skilled in theart), antimicrobial agents (e.g., preferably silver nanoparticles), abioactive agent, leachable lubricants, leachable tear-stabilizingagents, and mixtures thereof, as known to a person skilled in the art.

In accordance with a preferred embodiment of the invention, a preformedsilicone hydrogel contact lens of the invention can further comprise(but preferably comprises) repeating units of one or more UV-absorbingvinylic monomers and optionally (but preferably) one or moreUV/HEVL-absorbing vinylic monomers. The term “UV/HEVL-absorbing vinylicmonomer” refers to a vinylic monomer that can absorb UV light andhigh-energy-violet-light (i.e., light having wavelength between 380 nmand 440 nm.

Any suitable UV-absorbing vinylic monomers and UV/HEVL-absorbing vinylicmonomers can be used in a polymerizable composition for preparing apreformed SiHy contact lens of the invention. Examples of preferredUV-absorbing and UV/HEVL-absorbing vinylic monomers include withoutlimitation: 2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole,2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole,2-(2-hydroxy-3-methacrylamido methyl-5-tert octylphenyl) benzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-methoxybenzotriazole,2-(2′-hydroxy-5′-methacryloxypropyl-3′-t-butylphenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacryloxypropylphenyl) benzotriazole,2-hydroxy-5-methoxy-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzylmethacrylate (WL-1),2-hydroxy-5-methoxy-3-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)benzylmethacrylate (WL-5),3-(5-fluoro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzylmethacrylate (WL-2),3-(2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzylmethacrylate (WL-3),3-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-2-hydroxy-5-methoxybenzylmethacrylate (WL-4),2-hydroxy-5-methoxy-3-(5-methyl-2H-benzo[d][1,2,3]triazol-2-yl)benzylmethacrylate (WL-6),2-hydroxy-5-methyl-3-(5-(trifluoromethyl)-2H-benzo[d][1,2,3]triazol-2-yl)benzylmethacrylate (WL-7),4-allyl-2-(5-chloro-2H-benzo[d][1,2,3]triazol-2-yl)-6-methoxyphenol(WL-8),2-{2′-Hydroxy-3′-tert-5′[3″-(4″-vinylbenzyloxy)propoxy]phenyl}-5-methoxy-2H-benzotriazole,phenol,2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-ethenyl-(UVAM),2-[2′-hydroxy-5′-(2-methacryloxyethyl)phenyl)]-2H-benzotriazole(2-Propenoic acid, 2-methyl-,2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl]ethyl ester, Norbloc),2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-2H-benzotriazole,2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-methoxy-2H-benzotriazole(UV13),2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-chloro-2H-benzotriazole(UV28),2-[2′-Hydroxy-3′-tert-butyl-5′-(3′-acryloyloxypropoxy)phenyl]-5-trifluoromethyl-2H-benzotriazole(UV23), 2-(2′-hydroxy-5-methacrylamidophenyl)-5-methoxybenzotriazole(UV6), 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV9),2-(2-Hydroxy-3-methallyl-5-methylphenyl)-2H-benzotriazole (UV12),2-3′-t-butyl-2′-hydroxy-5′-(3″-dimethylvinylsilylpropoxy)-2′-hydroxyphenyl)-5-methoxybenzotriazole(UV15),2-(2′-hydroxy-5′-methacryloylpropyl-3′-tert-butylphenyl)-5-methoxy-2H-benzotriazole(UV16),2-(2′-hydroxy-5′-acryloylpropyl-3′-tert-butylphenyl)-5-methoxy-2H-benzotriazole(UV16A), 2-Methylacrylic acid3-[3-tert-butyl-5-(5-chlorobenzotriazol-2-yl)-4-hydroxyphenyl]-propylester (16-100, CAS#96478-15-8),2-(3-(tert-butyl)-4-hydroxy-5-(5-methoxy-2H-benzo[d][1,2,3]triazol-2-yl)phenoxy)ethylmethacrylate (16-102); Phenol,2-(5-chloro-2H-benzotriazol-2-yl)-6-methoxy-4-(2-propen-1-yl)(CAS#1260141-20-5);2-[2-Hydroxy-5-[3-(methacryloyloxy)propyl]-3-tert-butylphenyl]-5-chloro-2H-benzotriazole;Phenol, 2-(5-ethenyl-2H-benzotriazol-2-yl)-4-methyl-, homopolymer (9Cl)(CAS#83063-87-0). In accordance with the invention, the polymerizablecomposition comprises about 0.1% to about 3.0%, preferably about 0.2% toabout 2.5%, more preferably about 0.3% to about 2.0%, by weight of oneor more UV-absorbing vinylic monomers, related to the amount of allpolymerizable components in the polymerizable composition.

Where a vinylic monomer capable of absorbing ultra-violet radiation andhigh energy violet light (HEVL) is used in the invention, aGermane-based Norrish Type I photoinitiator and a light source includinga light in the region of about 400 to about 550 nm are preferably usedto initiate a free-radical polymerization. Any Germane-based NorrishType I photoinitiators can be used in this invention, so long as theyare capable of initiating a free-radical polymerization underirradiation with a light source including a light in the region of about400 to about 550 nm. Examples of Germane-based Norrish Type Iphotoinitiators are acylgermanium compounds described in U.S. Pat. No.7,605,190.

The bioactive agent is any compound that can prevent a malady in the eyeor reduce the symptoms of an eye malady. The bioactive agent can be adrug, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, aprotein, a nucleic acid, or any combination thereof. Examples of drugsuseful herein include, but are not limited to, rebamipide, ketotifen,olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine,lodoxamide, ketotifen, or the pharmaceutically acceptable salt or esterthereof. Other examples of bioactive agents include2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxyl acids (e.g.,glycolic, lactic, malic, tartaric, mandelic and citric acids and saltsthereof, etc.), linoleic and gamma linoleic acids, and vitamins (e.g.,B5, A, B6, etc.).

Examples of leachable lubricants include without limitation mucin-likematerials (e.g., polyglycolic acid) and non-crosslinkable hydrophilicpolymers (i.e., without ethylenically unsaturated groups). Anyhydrophilic polymers or copolymers without any ethylenically unsaturatedgroups can be used as leachable lubricants. Preferred examples ofnon-crosslinkable hydrophilic polymers include, but are not limited to,polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, ahomopolymer of a vinyl lactam, a copolymer of at least one vinyl lactamin the presence or in the absence of one or more hydrophilic vinyliccomonomers, a homopolymer of acrylamide or methacrylamide, a copolymerof acrylamide or methacrylamide with one or more hydrophilic vinylicmonomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), apolyoxyethylene derivative, poly-N-N-dimethylacrylamide, polyacrylicacid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides,and mixtures thereof. The number average molecular weight Mn of thenon-crosslinkable hydrophilic polymer is preferably from 5,000 to1,000,000.

Examples of leachable tear-stabilizing agents include, withoutlimitation, phospholipids, monoglycerides, diglycerides, triglycerides,glycolipids, glyceroglycolipids, sphingolipids, sphingo-glycolipids,fatty alcohols, fatty acids, mineral oils, and mixtures thereof.Preferably, a tear stabilizing agent is a phospholipid, a monoglyceride,a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, asphingolipid, a sphingo-glycolipid, a fatty acid having 8 to 36 carbonatoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixturethereof.

A polymerizable composition (SiHy lens formulation) can be a solventlessclear liquid prepared by mixing all polymerizable components and othernecessary component or a solution prepared by dissolving all of thedesirable components in any suitable solvent, such as, a mixture ofwater and one or more organic solvents miscible with water, an organicsolvent, or a mixture of one or more organic solvents, as known to aperson skilled in the art. The term “solvent” refers to a chemical thatcannot participate in free-radical polymerization reaction.

A solventless lens SiHy lens formulation typically comprises at leastone blending vinylic monomer as a reactive solvent for dissolving allother polymerizable components of the solventless SiHy lens formulation.Examples of preferred blending vinylic monomers include C₁-C₁₀ alkyl(meth)acrylate (e.g., methyl (meth)acrylate, ethyl (meth)acrylate,propyl (meth)acrylate, isopropyl (meth)acrylate, 2-ethylhexyl(meth)acrylate, pentyl (meth)acrylate, hexyl (meth)acrylate, etc.),cyclopentylacrylate, cyclohexylmethacrylate, cyclohexylacrylate,isobornyl (meth)acrylate, styrene, 4,6-trimethylstyrene (TMS), t-butylstyrene (TBS), trifluoroethyl (meth)acrylate, hexafluoro-isopropyl(meth)acrylate, hexafluorobutyl (meth)acrylate, or combinations thereof.Preferably, methyl methacrylate is used as a blending vinylic monomer inpreparing a solventless SiHy lens formulation.

Any solvents can be used in the invention. Example of preferred organicsolvents includes without limitation, tetrahydrofuran, tripropyleneglycol methyl ether, dipropylene glycol methyl ether, ethylene glycoln-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.),diethylene glycol n-butyl ether, diethylene glycol methyl ether,ethylene glycol phenyl ether, propylene glycol methyl ether, propyleneglycol methyl ether acetate, dipropylene glycol methyl ether acetate,propylene glycol n-propyl ether, dipropylene glycol n-propyl ether,tripropylene glycol n-butyl ether, propylene glycol n-butyl ether,dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether,propylene glycol phenyl ether dipropylene glycol dimethyl ether,polyethylene glycols, polypropylene glycols, ethyl acetate, butylacetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate,methylene chloride, 2-butanol, 1-propanol, 2-propanol, menthol,cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol,2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol,2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amylalcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol,3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol,2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol,2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol,4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol,3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol,3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol,4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol,1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol,3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol,2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol,2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol,1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol,1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethyl formamide,dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone, andmixtures thereof.

Numerous SiHy lens formulations have been described in numerous patentsand patent applications published by the filing date of this applicationand have been used in producing commercial SiHy contact lenses. Examplesof commercial SiHy contact lenses include, without limitation,asmofilcon A, balafilcon A, comfilcon A, delefilcon A, efrofilcon A,enfilcon A, fanfilcon A, galyfilcon A, lotrafilcon A, lotrafilcon B,narafilcon A, narafilcon B, senofilcon A, senofilcon B, senofilcon C,smafilcon A, somofilcon A, and stenfilcon A.

A SiHy lens formulation (i.e., polymerizable composition) can be cured(polymerized) thermally or actinically as known to a person skilled inthe art, preferably in molds for cast molding of contact lenses.

The thermal polymerization is carried out conveniently, for example at atemperature of from 25 to 120° C. and preferably 40 to 100° C. Thereaction time may vary within wide limits, but is conveniently, forexample, from 1 to 24 hours or preferably from 2 to 12 hours. It isadvantageous to previously degas the components and solvents used in thepolymerization reaction and to carry out said copolymerization reactionunder an inert atmosphere, for example under a nitrogen or argonatmosphere.

The actinic polymerization can then be triggered off by actinicradiation, for example light, in particular UV light or visible light ofa suitable wavelength. The spectral requirements can be controlledaccordingly, if appropriate, by addition of suitable photosensitizers.

In a preferred embodiment, the preformed contact lens comprises asilicone hydrogel bulk material which comprises: (1) repeating units ofat least one polysiloxane vinylic monomer (preferably selected fromthose described above); (2) repeating units of at least one hydrophilicvinylic monomer (preferably selected from those described above); (3)repeating units of at least one polysiloxane vinylic crosslinker(preferably selected from those described above); (4) repeating units ofat least one hydrophilic N-vinyl amide monomer (preferably selected fromthose described above); (5) repeating units of at least onepolycarbosiloxane vinylic monomer (preferably selected from thosedescribed above); (6) repeating units of at least one polycarbosiloxanevinylic crosslinker (preferably selected from those described above);(7) repeating units of at least one silicone-containing vinylic monomerhaving a bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silylgroup (preferably selected from those described above); (8) repeatingunits of one or more blending vinylic monomers (preferably selected fromthose described above); (9) repeating units of one or more non-siliconevinylic crosslinking agents (preferably selected from those describedabove); or (10) combinations thereof.

In a preferred embodiment, the preformed contact lens is a commercialSiHy contact lens (any one described above).

In accordance any one of the preferred embodiments of the invention, thepreformed silicone hydrogel contact lens is naturally wettable withoutbeing subjected to any post-curing surface treatment. Naturally-wettablepreformed SiHy contact lenses are disclosed in U.S. Pat. Nos. 6,367,929,6,822,016, 7,052,131, 7,249,848, 6,867,245, 7,268,198, 7,540,609,7,572,841, 7,750,079, 7,934,830, 8,231,218, 8,367,746, 8,445,614,8,481,662, 8,487,058, 8,513,325, 8,703,891, 8,820,928, 8,865,789,8,937,110, 8,937,111, 9,057,821, 9,057,822, 9,121,998, 9,125,808,9,140,825, 9,140,908, 9,156,934, 9,164,298, 9,170,349, 9,188,702,9,217,813, 9,296,159, 9,322,959, 9,322,960, 9,360,594, and 9,529,119;and in U.S. patent application Ser. Nos. 16/000,930 and 16/000,933.

In accordance with the invention, the preformed silicone hydrogelcontact lens has an oxygen permeability of at least about 50, preferablyat least about 60, more preferably at least about 70, even morepreferably at least about 90 barrers, most preferably at least about 110Barrers. The preformed silicone hydrogel contact lens can also have anequilibrium water content of from about 10% to about 70%, preferablyfrom about 10% to about 65%, more preferably from about 10% to about60%; even more preferably from about 15% to about 55%, most preferablyfrom about 15% to about 50% by weight. The preformed silicone hydrogelcontact lens can further have a bulk elastic modulus or bulk YoungModulus (hereinafter the terms, “softness,” “elastic modulus,” and“Young's modulus” are interchangeably used in this application to meanbulk elastic modulus if the term is not modified by the word “surface.”)of from about 0.3 MPa to about 1.8 MPa, preferably from 0.4 MPa to about1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa. A personskilled in the art knows well how to determine the elastic modulus andwater content of a silicone hydrogel material or a SiHy contact lens.For example, all commercial SiHy contact lenses have reported values ofoxygen permeability, elastic modulus and water content.

In any one of the preferred embodiments described above, a preformedcontact lens has a UVB transmittance of about 10% or less (preferablyabout 5% or less, more preferably about 2.5% or less, even morepreferably about 1% or less) between 280 nm and 315 nm, a UVAtransmittance of about 30% or less (preferably about 20% or less, morepreferably about 10% or less, even more preferably about 5% or less)between 315 nm and 380 nm, and a violet transmittance of from 0% toabout 70%, preferably from 5% to about 60%, more preferably from 5% toabout 50%, even more preferably from about 5% to about 40% between 380and 440 nm.

In accordance with the invention, contacting of a preformed contact lenswith a solution of a polyanionic polymer can occur by dipping it intothe coating solution or by spraying it with the coating solution. Onecontacting process involves solely dipping the preformed contact lens ina bath of a coating solution for a period of time or alternativelydipping the preformed contact lens sequentially in a series of bath ofcoating solutions for a fixed shorter time period for each bath. Anothercontacting process involves solely spray a coating solution. However, anumber of alternatives involve various combinations of spraying- anddipping-steps may be designed by a person having ordinary skill in theart.

Any polyanionic polymers can be used in forming an anchor layer on apreformed contact lens, so long as they contain at least 60% by mole ofrepeating units of one or more carboxyl-containing acrylic monomers (anyone of those described above). Examples of preferred polyanionicpolymers include without limitations polyacrylic acid, polymethacrylicacid, poly(ethylacrylic acid), poly(acrylic acid-co-methacrylic acid),poly[ethylacrylic acid-co-(meth)acrylic acid],poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylicacid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone],poly[ethylacrylic acid-co-acrylamide], poly[ethylacrylicacid-co-vinylpyrrolidone], poly[(meth)acrylic acid-co-vinylacetate],poly[ethylacrylic acid-co-vinylacetate], or combinations thereof.Preferably, a polyanionic polymer is polyacrylic acid, polymethacrylicacid, or a combination thereof.

In accordance with the invention, the number average molecular weight Mnof a polyanionic polymer for forming an anchor layer (or base coating)on preformed contact lenses is at least about 25,000 Daltons, preferablyat least about 50,000 Daltons, more preferably from about 100,000Daltons to about 5,000,000 Daltons.

A solution of a polyanionic polymer for forming an anchor layer (or basecoating) on preformed contact lenses can be prepared by dissolving oneor more polyanionic polymers in water, a mixture of water and one ormore organic solvents miscible with water, an organic solvent, or amixture of one or more organic solvent. Preferably, the polyanionicpolymer is dissolved in a mixture of water and one or more organicsolvents, an organic solvent, or a mixture of one or more organicsolvent. It is believed that a solvent system containing at least oneorganic solvent can swell a preformed contact lens so that a portion ofthe polyanionic polymer may penetrate into the preformed contact lensand increase the durability and thickness of the anchor layer (basecoating). Any organic solvents described above can be used inpreparation of a solution of the polyanionic polymer, so long as it candissolve the polyanionic polymer.

The concentration of polyanionic polymer is from about 0.001% to about1.5%, preferably from about 0.002% to about 0.75%, more preferably from0.003% to about 0.1% by weight relative to the total weight of thesolution.

As known to a person skilled in the art, the thickness of the anchorlayer (base coating) can be adjusted by varying the concentration of thepolyanionic polymer, the contacting time of the preformed contact lenswith the solution of the polyanionic polymer, the solvent system (e.g.,the amount of one or more organic solvents), pH or ionic strength of thesolution, or combinations thereof.

In accordance with the invention, any graft polymerization techniquesknown to a person skilled in the art can be used in grafting apolyanionic polymer onto the surface of a preformed contact lens.Preferably, a graft-from technique is used in the invention. Forexample, a preformed contact lens in dry state is first subjected to aplasma treatment in a plasma atmosphere of a compound having at leastone reactive functional group (e.g., a vinylic monomer having a primaryor secondary amino group, a carboxyl group, an epoxy group, an azlactonegroup, an aziridine group, or an isocyanate group) to form a plasmacoating having reactive functional groups. The plasma-treated contactlens is reacted with a compound having a free-radical initiator moiety(e.g., a thermal initiator or a photoinitiator) or preferably a livingpolymerization initiator moiety (e.g., an atom transfer radicalpolymerization (ATRP) initiator or a reversible addition fragmentationchain transfer polymerization (RAFT) initiator) and a functional groupco-reactive with the functional groups of the plasma coating on thecontact lens in the presence or absence of a coupling agent undercoupling reaction conditions known to a person skilled in the art. Theobtained contact lens with free-radical initiator moieties thereon isimmersed in a solution of one or more carboxyl-containing vinylicmonomers (preferably those carboxyl-containing acrylic monomersdescribed above) and optionally one or more other hydrophilic vinylicmonomer, and subject to conditions to initiate free radicalpolymerization of those carboxyl-containing vinylic monomers and othervinylic monomers so as to form a layer of a graft-from polyanionicpolymer of the carboxyl-containing vinylic monomers and optionally otherhydrophilic vinylic monomers.

In accordance with the invention, the thermally-crosslinkablehydrophilic polymeric material for forming the outer surface hydrogellayer (i.e., the crosslinked hydrophilic coating) comprisescrosslinkable groups, preferably thermally-crosslinkable groups (e.g.,epoxy groups, azetidinium groups, or combinations thereof), morepreferably azetidinium groups. Preferably, the water-soluble andcrosslinkable hydrophilic polymeric material is a partially-crosslinkedpolymeric material that comprises a three-dimensional network andthermally-crosslinkable groups, preferably azetidinium groups within thenetwork or being attached to the network. The term“partially-crosslinked” in reference to a polymeric material means thatthe crosslinkable groups of starting materials for making the polymericmaterial in crosslinking reaction have not been fully consumed. Forexample, such a thermally-crosslinkable hydrophilic polymeric materialcomprises azetidinium groups and is a partial reaction product of atleast one azetidinium-containing polymer with at least onehydrophilicity-enhancing agent (i.e., a wetting agent) having at leastone carboxyl, primary amine, secondary amine, or thiol group, accordingto the crosslinking reactions shown in Scheme I

in which X₁ is —S—*, —OC(═O)—*, or —NR′—* in which R′ is hydrogen or aC₁-C₂₀ unsubstituted or substituted alkyl group, and * represents anorganic radical.

Any suitable azetidinium-containing polymers can be used in theinvention. Examples of azetidinium-containing polymers includes withoutlimitation epichlorohydrin-functionalized polyamines, homopolymers of anazetidinium-containing vinylic monomer, copolymers of anazetidinium-containing vinylic monomer with one or more vinylicmonomers.

Preferably, an azetidinium-containing polymer is anepichlorohydrin-functionalized polyamine. Anepichlorohydrin-functionalized polyamine can be obtained by reactingepichlorohydrin with a polyamine polymer or a polymer containingsecondary amino groups. For example, a poly(alkylene imines) or apoly(amidoamine) which is a polycondensate derived from a polyamine anda dicarboxylic acid (e.g., adipic acid-diethylenetriamine copolymers)can react with epichlorohydrin to form an epichlorohydrin-functionalizedpolymer; a homopolymer or copolymer of mono-alkylaminoalkyl(meth)acrylate or mono-alkylaminoalkyl (meth)acrylamide can also reactwith epichlorohydrin to form an epichlorohydrin-functionalizedpolyamine; a poly(2-oxazoline-co-ethyleneimine) copolymer can react withepichlorohydrin to form an epichlorohydrin-functionalized polyamine(i.e., a poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin). Thereaction conditions for epichlorohydrin-functionalization of a polyamineor polyamidoamine polymer are taught in EP1465931 (herein incorporatedby reference in its entirety). A preferredepichlorohydrin-functionalized polyamine ispolyamidoamine-epichlorohydrin (PAE) or apoly(2-oxazoline-co-ethyleneimine)-epichlorohydrin.

Polyamidoamine-epichlorohydrin is commercially available, such as, forexample, Kymene® or Polycup® resins (epichlorohydrin-functionalizedadipic acid-diethylenetriamine copolymers) from Hercules.

Poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin can be preparedaccording to procedures described in U.S. Pat. Appl. Pub. No. US2016/0061995 A1.

Homopolymers and copolymers of an azetidinium-containing vinylic monomercan be obtained according to the procedures described in U.S. Pat. Appl.Pub. No. 2013/0337160A1.

Any suitable hydrophilicity-enhancing agents can be used in theinvention so long as they are ophthalmically compatible and contain atleast one amino group, at least one carboxyl group, and/or at least onethiol group, preferably contain at least one carboxyl group, at leastone thiol group, or combinations thereof.

A preferred class of hydrophilicity-enhancing agents include withoutlimitation: primary amino-, secondary amino-, carboxyl- orthiol-containing monosaccharides (e.g., 3-amino-1,2-propanediol,1-thiolglycerol, 5-keto-D-gluconic acid, galactosamine, glucosamine,galacturonic acid, gluconic acid, glucosaminic acid, mannosamine,saccharic acid 1,4-lactone, saccharide acid, Ketodeoxynonulosonic acid,N-methyl-D-glucamine, 1-amino-1-deoxy-3-D-galactose,1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethylgluconamide); primary amino-, secondary amino-, carboxyl- orthiol-containing disaccharides (e.g., chondroitin disaccharide sodiumsalt, di(f-D-xylopyranosyl)amine, digalacturonic acid, heparindisaccharide, hyaluronic acid disaccharide, Lactobionic acid); andprimary amino-, secondary amino-, carboxyl- or thiol-containingoligosaccharides (e.g., carboxymethyl-3-cyclodextrin sodium salt,trigalacturonic acid); and combinations thereof.

Another preferred class of hydrophilicity-enhancing agents ishydrophilic polymers having one or more (primary or secondary) amino,carboxyl and/or thiol groups. More preferably, the content of the amino(—NHR′ with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH)groups in a hydrophilic polymer as a hydrophilicity-enhancing agent isless than about 40%, preferably less than about 30%, more preferablyless than about 20%, even more preferably less than about 10%, by weightbased on the total weight of the hydrophilic polymer.

One preferred class of hydrophilic polymers as hydrophilicity-enhancingagents are (primary or secondary) amino- or carboxyl-containingpolysaccharides, for example, such as, carboxymethylcellulose (having acarboxyl content of about 40% or less, which is estimated based on thecomposition of repeating units, —[C₆H_(10-m)O₅(CH₂CO₂H)_(m)]— in which mis 1 to 3), carboxyethylcellulose (having a carboxyl content of about36% or less, which is estimated based on the composition of repeatingunits, —[C₆H_(10-m)O₅(C₂H₄CO₂H)_(m)]— in which m is 1 to 3)carboxypropylcellulose (having a carboxyl content of about 32% or less,which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(C₃H₆CO₂H)_(m)]—, in which m is 1 to 3), hyaluronic acid(having a carboxyl content of about 11%, which is estimated based on thecomposition of repeating units, —(C₁₃H₂₀O₉NCO₂H)—), chondroitin sulfate(having a carboxyl content of about 9.8%, which is estimated based onthe composition of repeating units, —(C₁₂H₁₈O₁₃NS CO₂H)—), orcombinations thereof.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents include without limitation:poly(ethylene glycol) (PEG) with mono-amino (primary or secondaryamino), carboxyl or thiol group (e.g., PEG-NH₂, PEG-SH, PEG-COOH);H₂N-PEG-NH₂; HOOC-PEG-COOH; HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH;H₂N-PEG-SH; multi-arm PEG with one or more amino (primary or secondary),carboxyl or thiol groups; PEG dendrimers with one or more amino (primaryor secondary), carboxyl or thiol groups; a diamino-(primary orsecondary) or dicarboxyl-terminated homo- or co-polymer of anon-reactive hydrophilic vinylic monomer; a monoamino-(primary orsecondary) or monocarboxyl-terminated homo- or co-polymer of anon-reactive hydrophilic vinylic monomer; a copolymer which is apolymerization product of a composition comprising (1) about 60% byweight or less, preferably from about 0.1% to about 30%, more preferablyfrom about 0.5% to about 20%, even more preferably from about 1% toabout 15%, by weight of one or more reactive vinylic monomers and (2) atleast one non-reactive hydrophilic vinylic monomer; and combinationsthereof.

In accordance with the invention, reactive vinylic monomers can becarboxyl-containing vinylic monomers, primary amino-containing vinylicmonomers, or secondary amino-containing vinylic monomers.

Examples of preferred carboxyl-containing vinylic monomers includewithout limitation acrylic acid, methacrylic ethylacrylic acid,N-2-(meth)acrylamidoglycolic acid, and combinations thereof.

Examples of preferred primary and secondary amino-containing vinylicmonomers include without limitation N-2-aminoethyl (meth)acrylamide,N-2-methylaminoethyl (meth)acrylamide, N-2-ethylaminoethyl(meth)acrylamide, N-3-aminopropyl (meth)acrylamide,N-3-methylaminopropyl (meth)acrylamide, 2-aminoethyl (meth)acrylate,2-methylaminoethyl (meth)acrylate, 2-ethylaminoethyl (meth)acrylate,3-aminopropyl (meth)acrylate, 3-methylaminopropyl (meth)acrylate,3-ethylaminopropyl (meth)acrylate, 3-amino-2-hydroxypropyl(meth)acrylate, and combinations thereof.

In accordance with the invention, a non-reactive vinylic monomer is avinylic monomer free of any carboxyl group, primary amino group,secondary amino group, epoxide group, isocyanate group, azlactone group,or aziridine group. Non-reactive vinylic monomers preferably arenon-charged hydrophilic vinylic monomers which are free of carboxyl oramino group (any those described above can be used here),phosphorylcholine-containing vinylic monomers (any those described abovecan be used here), or combinations thereof.

More preferably, a hydrophilic polymer as a hydrophilicity-enhancingagent is:

a poly(ethylene glycol) having one sole functional group of —NH₂, —SH or—COOH;

a poly(ethylene glycol) having two terminal functional groups selectedfrom the group consisting of —NH₂, —COOH, —SH, and combinations thereof;

a multi-arm poly(ethylene glycol) having one or more functional groupsselected from the group consisting of —NH₂, —COOH, —SH, and combinationsthereof;

a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymer of a non-reactive hydrophilic vinylic monomer;

a copolymer which is a polymerization product of a compositioncomprising (1) from about 0.1% to about 30%, preferably from about 0.5%to about 20%, more preferably from about 1% to about 15%, by weight ofacrylic acid, methacrylic acid, ethylacrylic acid,2-(meth)acrylamidoglycolic acid, N-2-aminoethyl (meth)acrylamide,N-2-methylaminoethyl (meth)acrylamide, N-2-ethylaminoethyl(meth)acrylamide, N-3-aminopropyl (meth)acrylamide,N-3-methylaminopropyl (meth)acrylamide, 2-aminoethyl (meth)acrylate,2-methylaminoethyl (meth)acrylate, 2-ethylaminoethyl (meth)acrylate,3-aminopropyl (meth)acrylate, 3-methylaminopropyl (meth)acrylate,3-amino-2-hydroxypropyl (meth)acrylate, or a combination thereof, and(2) at least one non-reactive hydrophilic vinylic monomer selected fromthe group consisting of acryamide, N,N-dimethylacrylamide,N-vinylpyrrolidone, (meth)acryloyloxyethyl phosphorylcholine,N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl(meth)acrylate, N-hydroxyethyl (meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol, and combination thereof,

wherein the non-reactive hydrophilic vinylic monomer selected from thegroup consisting of selected from the group consisting of alkyl(meth)acrylamides (any one described above), N-2-dimethylaminoethyl(meth)acrylamide, dimethylaminoethyl (meth)acrylate, hydroxyl-containingacrylic monomers (any one described above), N-vinyl amide monomers (anyone described above), methylene-containing pyrrolidone monomers (i.e.,pyrrolidone derivatives each having a methylene group connected to thepyrrolidone ring at 3- or 5-position) (any one described above), acrylicmonomers having a C₁-C₄ alkoxyethoxy group (any one described above),vinyl ether monomers (any one described above), allyl ether monomers(any one described above), a phosphorylcholine-containing vinylicmonomer (any one described above) and combinations thereof (preferablyselected from the group consisting of (meth)acryloyloxyethylphosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine,4-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate,2-[(meth)acryloylamino]ethyl-2′-(trimethylammonio)ethylphosphate,3-[(meth)acryloylamino]propyl-2′-(trimethylammonio)ethylphosphate,4-[(meth)acryloylamino]butyl-2′-(trimethylammonio)ethylphosphate,(meth)acrylamide, dimethyl (meth)acrylamide, N-2-hydroxylethyl(meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide,N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, 2-hydroxyethyl (meth)acrylate, glycerol methacrylate(GMA), tetra(ethylene glycol) (meth)acrylate, poly(ethylene glycol)ethyl(meth)acrylamide having a number average molecular weight of up to 1500,poly(ethylene glycol) (meth)acrylate having a number average molecularweight of up to 1500, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide,N-vinyl formamide, N-vinyl acetamide,1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, tetra(ethylene glycol) methyl ether(meth)acrylate, methoxypoly(ethylene glycol)ethyl (meth)acrylamidehaving a number average molecular weight of up to 1500, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500, tetra(ethylene glycol) monovinyl ether,poly(ethylene glycol) monovinyl ether, tetra(ethylene glycol) methylvinyl ether, poly(ethylene glycol) methyl vinyl ether, tetra(ethyleneglycol) monoallyl ether, poly(ethylene glycol) monoallyl ether,tetra(ethylene glycol) methyl allyl ether, poly(ethylene glycol) methylallyl ether, vinyl alcohol, allyl alcohol, and combinations thereof,more preferably selected from the group consisting of(meth)acryloyloxyethyl phosphorylcholine, (meth)acryloyloxypropylphosphorylcholine,4-((meth)acryloyloxy)butyl-2′-(trimethylammonio)ethylphosphate,2-[(meth)acryloylamino]ethyl-2′-(trimethylammonio)ethylphosphate,3-[(meth)acryloylamino]propyl-2′-(trimethylammonio)ethylphosphate,4-[(meth)acryloylamino]butyl-2′-(trimethylammonio)ethylphosphate,(meth)acrylamide, dimethyl (meth)acrylamide, N-2-hydroxylethyl(meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide,N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, 2-hydroxyethyl (meth)acrylate, glycerol methacrylate(GMA), poly(ethylene glycol)ethyl (meth)acrylamide having a numberaverage molecular weight of up to 1500, poly(ethylene glycol)(meth)acrylate having a number average molecular weight of up to 1500,N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, methoxypoly(ethyleneglycol)ethyl (meth)acrylamide having a number average molecular weightof up to 1500, methoxy polyethylene glycol (meth)acrylate having aweight average molecular weight of up to 1500, poly(ethylene glycol)monovinyl ether, poly(ethylene glycol) methyl vinyl ether, poly(ethyleneglycol) monoallyl ether, poly(ethylene glycol) methyl allyl ether, vinylalcohol, allyl alcohol, and combinations thereof, even more preferablyselected from the group consisting of (meth)acryloyloxyethylphosphorylcholine, (meth)acryloyloxypropyl phosphorylcholine,2-[(meth)acryloylamino]ethyl-2′-(trimethylammonio)ethylphosphate,3-[(meth)acryloylamino]propyl-2′-(trimethylammonio)ethylphosphate,(meth)acrylamide, dimethyl (meth)acrylamide, N-2-hydroxylethyl(meth)acrylamide, N,N-bis(hydroxyethyl) (meth)acrylamide,N-2,3-dihydroxypropyl (meth)acrylamide, N-tris(hydroxymethyl)methyl(meth)acrylamide, poly(ethylene glycol)ethyl (meth)acrylamide having anumber average molecular weight of up to 1500, poly(ethylene glycol)(meth)acrylate having a number average molecular weight of up to 1500,N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, methoxypoly(ethyleneglycol)ethyl (meth)acrylamide having a number average molecular weightof up to 1500, methoxy polyethylene glycol (meth)acrylate having aweight average molecular weight of up to 1500, and combinations thereof.

PEGs with functional groups and multi-arm PEGs with functional groupscan be obtained from various commercial suppliers, e.g., CreativePEGWorks, Polyscience, and Shearwater Polymers, etc.

Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymers of one or more non-reactive hydrophilic vinylic monomers orof a phosphorylcholine-containing vinylic monomer can be preparedaccording to procedures described in U.S. Pat. No. 6,218,508. Forexample, to prepare a diamino- or dicarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer, thenon-reactive vinylic monomer, a chain transfer agent with an amino orcarboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropionic acid,thioglycolic acid, thiolactic acid, or other hydroxymercaptanes,aminomercaptans, or carboxyl-containing mercaptanes) and optionallyother vinylic monomer are copolymerized (thermally or actinically) witha reactive vinylic monomer (having an amino or carboxyl group), in thepresence of an free-radical initiator. Generally, the molar ratio ofchain transfer agent to that of all of vinylic monomers other than thereactive vinylic monomer is from about 1:5 to about 1:100, whereas themolar ratio of chain transfer agent to the reactive vinylic monomer is1:1. In such preparation, the chain transfer agent with amino orcarboxyl group is used to control the molecular weight of the resultanthydrophilic polymer and forms a terminal end of the resultanthydrophilic polymer so as to provide the resultant hydrophilic polymerwith one terminal amino or carboxyl group, while the reactive vinylicmonomer provides the other terminal carboxyl or amino group to theresultant hydrophilic polymer. Similarly, to prepare a monoamino- ormonocarboxyl-terminated homo- or co-polymer of a non-reactivehydrophilic vinylic monomer, the non-reactive vinylic monomer, a chaintransfer agent with an amino or carboxyl group (e.g.,2-aminoethanethiol, 2-mercaptopropionic acid, thioglycolic acid,thiolactic acid, or other hydroxymercaptanes, aminomercaptans, orcarboxyl-containing mercaptanes) and optionally other vinylic monomersare copolymerized (thermally or actinically) in the absence of anyreactive vinylic monomer.

Copolymers comprising a non-reactive hydrophilic vinylic monomer and areactive vinylic monomer (e.g., a carboxyl-containing vinylic monomer, aprimary amino group-containing vinylic monomer or a secondary aminogroup-containing vinylic monomer) can be prepared according to anywell-known radical polymerization methods or obtained from commercialsuppliers. Copolymers containing methacryloyloxyethyl phosphorylcholineand carboxyl-containing vinylic monomer (or amino-containing vinylicmonomer) can be obtained from NOF Corporation (e.g., LIPIDURE®-A and-AF) or prepared according to the procedures described in U.S. Pat. No.9,127,099.

The weight average molecular weight M_(w) of the hydrophilic polymerhaving at least one amino, carboxyl or thiol group (as ahydrophilicity-enhancing agent) is preferably from about 500 to about5,000,000, more preferably from about 1,000 to about 2,000,000, evenmore preferably from about 5,000 to about 1,000,000 Daltons.

Water-soluble and thermally-crosslinkable hydrophilic polymericmaterials can be prepared according to the processes disclosed in U.S.Pat. Appl. Pub. Nos. US 2016/0061995 A1 and US2013/0337160 A1 and inU.S. Pat. No. 8,529,057.

In a preferred embodiment, a water-soluble thermally-crosslinkablepolymeric material can be obtained by heating an aqueous reactivesolution, which comprises at least one azetidinium-containing polymerand at least one hydrophilicity-enhancing agent (i.e., a wetting agent)having at least one reactive functional group selected from the groupconsisting of amino group, carboxyl group, thiol group, and acombination thereof, to a temperature of from about 35° C. to about 85°C. and maintaining the temperature for a period of time sufficient(about 6 hours or less, preferably about 5 hours, more preferably fromabout 2 hour to about 4 hours). The aqueous reactive solution preferablycomprises from about 70 mM to about 170 mM (preferably about 90 mM toabout 150 mM, more preferably from about 100 mM to about 130 mM) of oneor more ionic compounds and a pH of at least 8.0 (preferably at least8.5, more preferably at least 9.0, even more preferably at least 9.5).It should be understood that the reaction time should be long enough tocovalently attach the hydrophilicity-enhancing agent onto the polymerchain of the azetidinium-containing polymer, but should be short enoughnot to consume all the azetidinium groups of the azetidinium-containingpolymer and not to form a gel (i.e., not water-soluble) due to the toomany crosslinkages formed between the azetidinium-containing polymer andthe hydrophilicity-enhancing agent. A resultant polymeric material is alightly-crosslinked polymeric material which has a highly-branchedstructure and still comprises thermally-crosslinkable azetidiniumgroups.

A person skilled in the art understands well how to adjust the pH of thereactive mixture, e.g., by adding a base (e.g., NaOH, KOH, NH₄OH, ormixture thereof) or an acid (e.g., HCl, H₂SO₄, H₃PO₄, citric acid,acetic acid, boric acid, or mixture thereof).

In accordance with the invention, any ionic compounds can be used in thereactive mixture. Preferably, ionic compounds are those used as ionictonicity-adjusting agents and ionic buffering agents used in anophthalmic solutions. Examples of preferred ionic tonicity-adjustingagents includes without limitation sodium chloride, potassium chloride,and combinations thereof. Examples of preferred ionic buffering agentsincludes various salts of phosphoric acid (e.g. NaH₂PO₄, Na₂HPO₄,Na₃PO₄, KH₂PO₄, K₂HPO₄, K₃PO₄, or mixtures thereof), various salts ofboric acid (e.g., sodium borate, potassium borate, or mixture thereof),various salts of citric acid (e.g., monosodium citrate, disodiumcitrate, trisodium citrate, monopotassium citrate, dipotassium citrate,tripotassium citrate, or mixtures thereof), various salts of carbonicacid (e.g., Na₂CO₃, NaHCO₃, K₂CO₃, KHCO₃, or mixture thereof).

The aqueous reactive solution for preparing a water-solublethermally-crosslinkable polymeric material can be prepared by dissolvinga desired amount of an azetidinium-containing polymer, a desired amountof a hydrophilicity-enhancing agent with at least one reactivefunctional group, and desired amounts of other components (e.g., ionicbuffering agents, ionic tonicity-adjusting agents, etc.) in water (or amixture of water and a minority amount of a water-soluble organicsolvent) to form an aqueous solution and then adjusting the pH of theaqueous solution if necessary.

In accordance with the invention, the concentration ratio of ahydrophilicity-enhancing agent relative to an azetidinium-containingpolymer in the aqueous reactive solution must be selected not to rendera resultant water-soluble thermally-crosslinkable polymeric materialwater-insoluble (i.e., a solubility of less than 0.005 g per 100 ml ofwater at room temperature) and not to consume more than about 99%,preferably about 98%, more preferably about 97%, even more preferablyabout 96% of the azetidinium groups of the azetidinium-containingpolymer.

In a preferred embodiment, the aqueous reactive solution comprises from0.01% to about 10% by weight (preferably from 0.05% to about 5% byweight, more preferably from 0.08% to about 1% by weight, even morepreferably from 0.1% to about 0.4% by weight) of anazetidinium-containing polymer and from about 0.01% to about 10% byweight (preferably from 0.02% to about 5% by weight, more preferablyfrom 0.05% to about 2% by weight, even more preferably from 0.08% toabout 1.0% by weight) of a hydrophilicity-enhancing agent having atleast one reactive function group (carboxyl, primary amino, secondaryamino group), the concentration ratio of the azetidinium-containingpolymer to the hydrophilicity-enhancing agent is from about 1000:1 to1:1000 (preferably from about 500:1 to about 1:500, more preferably fromabout 250:1 to about 1:250, even more preferably from about 100:1 toabout 1:100).

In a preferred embodiment, the water-soluble thermally-crosslinkablepolymeric material comprises (i) from about 20% to about 95% by weightof first polymer chains derived from a polyamidoamine-epichlorohydrin ora poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin, (ii) from about 5%to about 80% by weight of hydrophilic moieties or second polymer chainsderived from at least one hydrophilicity-enhancing agent having at leastone reactive functional group selected from the group consisting ofamino group, carboxyl group, thiol group, and combination thereof(preferably carboxyl or thiol groups), wherein the hydrophilic moietiesor second polymer chains are covalently attached to the first polymerchains through one or more covalent linkages each formed between oneazetidinium group of the polyamidoamine-epichlorohydrin or thepoly(2-oxazoline-co-ethyleneimine)-epichlorohydrin and one amino,carboxyl or thiol group of the hydrophilicity-enhancing agent, and (iii)azetidinium groups which are parts of the first polymer chains orpendant or terminal groups covalently attached to the first polymerchains. The composition of a chemically-modifiedpoly(2-oxazoline-co-ethyleneimine)-epichlorohydrin or achemically-modified polyamidoamine-epichlorohydrin is determined by thecomposition (based on the total weight of the reactants) of a reactantmixture used for such a polymer according to the crosslinking reactionsshown in Scheme I above. For example, if a reactant mixture comprisesabout 75% by weight of a polyamidoamine-epichlorohydrin and about 25% byweight of at least one hydrophilicity-enhancing agent based on the totalweight of the reactants, then the resultant chemically-modifiedpolyamidoamine-epichlorohydrin comprises about 75% by weight of firstpolymer chains derived from the polyamidoamine-epichlorohydrin and about25% by weight of hydrophilic moieties or second polymer chains derivedfrom said at least one hydrophilicity-enhancing agent.

Any polyaziridines can be used in the invention for neutralizing thenegative charges present in a water gradient contact lens. Examples ofpreferred polyaziridines include without limitation trimethylopropanetris(2-methyl-1-aziridinepropionate) (aka, PZ-28), pentaerythritoltris[3-(1-aziridinyl)propionate], trimethylopropanetris(3-aziridinopropionate) (aka, PZ-33), a Michael reaction product ofa vinylic crosslinker having at least three (meth)acryloyl groups and2-methylaziridine (or aziridine), and combinations thereof. Preferably,a polyaziridine comprising at least methyl-aziridinyl groups is used inthe invention.

Examples of preferred vinylic crosslinkers having at least three(meth)acryloyl groups include without limitation trimethylolpropanetriacrylate, pentaerythritol triacrylate,tris(2-hydroxyethyl)isocyanurate triacrylate, trimethylolpropaneethoxylate triacrylates (sold by Sartomer under the names SR454, SR499,SR502, SR9035 or SR415), glyceryl propoxylate triacrylate (sold bySartomer under the name SR9020), trimethylolpropane propoxylatetriacrylates (sold by Sartomer under the names SR492 and CD501),pentaerythritol tetraacrylate, ditrimethylolpropane tetraacrylate,pentaerythritol ethoxylate tetraacrylate (sold by Sartomer under thename SR494), dipentaerythritol pentaacrylate, caprolactone modifieddipentaerythritol hexaacrylates (sold by Sartomer under the namesKayarad DCPA-20 and DCPA60) or dipentaerythritol pentaacrylate (sold byUCB Chemicals under the name DPHPA). ethoxylated glycerol triacrylate,ethoxylated trimethylolpropane trimethacrylate, propoxylatedtrimethylolpropane trimethacrylate, ethoxylated pentaerythritoltrimethacrylate, ethoxylated pentaerythritol tetramethacrylate,ethoxylated dipentaerythritol trimethacrylate, ethoxylateddipentaerythritol tetramethacrylate, ethoxylated dipentaerythritolpentamethacrylate, ethoxylated dipentaerythritol hexamethacrylate,ethoxylated dipentaerythritol triacrylate, ethoxylated dipentaerythritoltetraacrylate, ethoxylated dipentaerythritol pentaacrylate, ethoxylateddipentaerythritol hexaacrylate, propoxylated pentaerythritoltrimethacrylate, propoxylated pentaerythritol triacrylate, propoxylatedpentaerythritol tetramethacrylate, propoxylated pentaerythritoltetraacrylate, propoxylated dipentaerythritol trimethacrylate,propoxylated dipentaerythritol tetramethacrylate, propoxylateddipentaerythritol pentamethacrylate, propoxylated dipentaerythritolhexamethacrylate, propoxylated dipentaerythritol triacrylate,propoxylated dipentaerythritol tetraacrylate, propoxylateddipentaerythritol pentaacrylate and propoxylated dipentaerythritolhexaacrylate, ethoxylated trimethyloylpropane triacrylamide (Examples 1of U.S. Pat. No. 9,011,884), and combinations thereof.

In any one of the above preferred embodiments, a process of theinvention further comprises a step of soaking the contact lens precursorin a second aqueous solution comprising at least one polyaziridinehaving a number average molecular weight of about 2000 Dalton or less(preferably from 250 Daltons to 1500 Daltons, more preferably from 300Dalton to 1000 Dalton, even more preferably from 350 Dalton to about 800Daltons) and at least two aziridine groups.

In any one of the above preferred embodiments, the first aqueoussolution further comprises at least one polyaziridine having a numberaverage molecular weight of about 2000 Dalton or less (preferably from250 Daltons to 1500 Daltons, more preferably from 300 Dalton to 1000Dalton, even more preferably from 350 Dalton to about 800 Daltons) andat least two aziridine groups.

In any one of the above preferred embodiments, the first and secondaqueous solutions independent of each other comprise two polyaziridines,the first polyaziridine having at least two aziridine groups of

and the second polyaziridine having at least two aziridine groups of

and at least one hydrophilic moiety selected from the group consistingof —OH, —OC₂H₄O—. —CONHR¹, —CONR¹—, and combinations thereof, wherein R¹is hydrogen, methyl or ethyl. It is believed that because a secondpolyaziridine with groups of

would react with carboxyl groups and hot water faster than a firstpolyaziridine with

does, the second polyaziridine would react first with carboxyl groups atand near the lens surface and the first polyaziridine would penetratedeeper to react with carboxyl groups buried deep in the outer surfacehydrogel layer and even the bulk material of the contact lens. Becausethe second polyaziridine is more hydrophilic than the firstpolyaziridine, it would have a minimal impact upon the hydrophilicityand wettability of the outer surface hydrogel layer.

In any one of the above preferred embodiments, the first and secondaqueous solutions independent of each other comprise from about 0.01% toabout 2.5% by weight (preferably from about 0.02% to about 2.0% byweight, more preferably from about 0.05% to about 1.0% by weight, evenmore preferably from about 0.05% to about 0.5% by weight) of at leastone polyaziridine (any of those described above).

In any one of the above preferred embodiments, the first and secondaqueous solutions independent of each other further comprises anitrogen-containing compound, preferably urea. A nitrogen-containingcompound can stabilize an aqueous solution of a polyaziridine andtherefore can prolong the shelf life of the solution of thepolyaziridine.

In accordance with the invention, the contact lens precursor with ananchor layer thereon is heated in a first aqueous solution whichcomprises at least one polyaziridine and at least onethermally-crosslinkable hydrophilic polymeric material havingazetidinium groups and optionally (but preferably) amino groups, thiolgroups, carboxyl groups or combinations thereof, at a temperature offrom about 60° C. to about 140° C. for a time period to crosslink thethermally-crosslinkable hydrophilic polymeric material while covalentlyattaching the crosslinked thermally-crosslinkable hydrophilic polymericmaterial onto the anchor layer so as to form an outer surface hydrogellayer, to convert a majority or most negatively-charged groups in thewater gradient contact lens into non-charged ester groups throughaziridine groups to minimize or eliminate uptake of a polycationicantimicrobial, and to crosslinked the anchor layer through apolyaziridine as a flexible crosslinker so as to enforce the durabilityof the outer surface hydrogel layer while having no or minimal adverseimpacts on the wettability, hydrophilicity, and lubricity of the outersurface hydrogel layer on the contact lens.

In any one of the above preferred embodiments, the step of heating isperformed by autoclaving the contact lens precursor with an anchor layerthereon immersed in the first aqueous coating solution which is apackaging solution in a sealed lens package at a temperature of fromabout 115° C. to about 125° C. for approximately 20-90 minutes. It isbelieved that during autoclave those azetidinium groups which do notparticipate in crosslinking reaction may be hydrolyzed into2,3-dihydroxypropyl (HO—CH—CH(OH)—CH₂—) groups and that theazetidinium-containing polymeric material present in the lens packagingsolution, if applicable, can be converted to a non-reactive polymericwetting agent capable of improving a lens's insert comfort. It is alsobelieved that during autoclave those aziridine groups which do notparticipate in crosslinking reaction may be hydrolyzed (i.e.,ring-opened) into hydroxyethylamino and/or 2-hydroxypropylamino groups.Consequently, the lens packaging solution is ophthalmically safe afterautoclave.

Preferably, the lens packaging solution further comprises a partiallyhydrolyzed polyvinyl alcohol having a hydrolysis degree of hydrolysis offrom about 80% to about 98%. It is believed that during autoclave alarge percentage of the vinylacetate monomeric units of a partiallyhydrolyzed polyvinyl alcohol would be hydrolyzed to form vinyl alcoholmonomeric units and acetic acid which in turn can react with any excessaziridine groups so as to ensure that no aziridine group can surviveafter autoclave and that the packaging solution after autoclave isophthalmically safe. Furthermore, a partially-hydrolyzed polyvinylalcohol can be a non-reactive polymeric wetting agent capable ofimproving a lens's insert comfort.

More preferably, the lens packaging solution further comprises apartially hydrolyzed polyvinyl alcohol having a hydrolysis degree ofhydrolysis of from about 80% to about 98% and urea. The advantages ofthe combination of the partially-hydrolyzed polyvinyl alcohol and theurea are that both substances can be hydrolyzed during autoclave, thatthe effects of their corresponding hydrolysis products (acetic acid fromthe partially hydrolyzed polyvinyl alcohol and ammonium from urea) onthe pH of the packaging solution after autoclave can be cancelled out,and that a partially-hydrolyzed polyvinyl alcohol can be a non-reactivepolymeric wetting agent capable of improving a lens's insert comfort.

In any one of the above preferred embodiments, the lens packagingsolution has a pH of from about 7.0 to about 9.0 before autoclaving anda pH of from about 6.5 to about 7.7 after autoclaving.

Lens packages (or containers) are well known to a person skilled in theart for autoclaving and storing a contact lens. Any lens packages can beused in the invention.

Preferably, a lens package is a blister package which comprises a baseand a cover, wherein the cover is detachably sealed to the base, whereinthe base includes a cavity for receiving a sterile packaging solutionand the contact lens.

Lenses are packaged in individual packages, sealed, and sterilized(e.g., by autoclave at about 120° C. or higher for at least 30 minutesunder pressure) prior to dispensing to users. A person skilled in theart will understand well how to seal and sterilize lens packages.

In accordance with the invention, a packaging solution contains at leastone buffering agent and one or more other ingredients known to a personskilled in the art. Examples of other ingredients include withoutlimitation, tonicity agents, surfactants, antibacterial agents,preservatives, and lubricants (e.g., cellulose derivatives, polyvinylalcohol, polyvinyl pyrrolidone).

The packaging solution contains a buffering agent in an amountsufficient to maintain a pH of the packaging solution in the desiredrange after autoclave, for example, preferably in a physiologicallyacceptable range of about 6.5 to about 7.7. Any known, physiologicallycompatible buffering agents can be used. Suitable buffering agents as aconstituent of the contact lens care composition according to theinvention are known to the person skilled in the art. Examples are boricacid, borates, e.g. sodium borate, citric acid, citrates, e.g. potassiumcitrate, bicarbonates, e.g. sodium bicarbonate, TRIS(2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris(Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane),bis-aminopolyols, triethanolamine, ACES(N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES(N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES(2-(N-morpholino)ethanesulfonic acid), MOPS(3-[N-morpholino]-propanesulfonic acid), PIPES(piperazine-N,N′-bis(2-ethanesulfonic acid), TES(N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), saltsthereof, phosphate buffers, e.g. Na₂HPO₄, NaH₂PO₄, and KH₂PO₄ ormixtures thereof. Preferably, the buffering agents are phosphatebuffers, borate buffers, or combinations thereof. The amount of eachbuffer agent in a packaging solution is preferably from 0.001% to 2%,preferably from 0.01% to 1%; most preferably from about 0.05% to about0.30% by weight.

The packaging solution has a tonicity of from about 200 to about 450milliosmol (mOsm), preferably from about 250 to about 350 mOsm. Thetonicity of a packaging solution can be adjusted by adding organic orinorganic substances which affect the tonicity. Suitable occularlyacceptable tonicity agents include, but are not limited to sodiumchloride, potassium chloride, glycerol, propylene glycol, polyols,mannitol, sorbitol, xylitol and mixtures thereof.

A packaging solution of the invention has a viscosity of from about 1centipoise to about 5 centipoises, at 25° C.

In a preferred embodiment, the packaging solution comprises: (1)preferably from about 0.01% to about 2%, more preferably from about0.05% to about 1.5%, even more preferably from about 0.1% to about 1%,most preferably from about 0.2% to about 0.5%, by weight of awater-soluble thermally-crosslinkable hydrophilic polymeric materialhaving azetidinium groups; and (2) from about 0.01% to about 2.5% byweight (preferably from about 0.05% to about 2.0% by weight, morepreferably from about 0.1% to about 2.0% by weight, even more preferablyfrom about 0.2% to about 1.5% by weight) of at least one polyaziridine(any of those described above).

In a preferred embodiment, the outer surface hydrogel layer has a highdigital-rubbing resistance as characterized by having no surfacecracking lines visible under dark field after the contact lens is rubbedbetween fingers. It is believed that digital-rubbing-induced surfacecracking may reduce the surface lubricity and/or may not be able preventsilicone from migrating onto the surface (exposure). Surface crackingmay also indicate excessive crosslinking density in the surface layerswhich may affect the surface elastic modulus. Preferably, thenon-silicone hydrogel material in the outer hydrogel layers (thecrosslinked coating) comprises crosslinkages derived from azetidiniumgroups in a thermally-induced coupling reaction.

In another preferred embodiment, the outer surface hydrogel layer has areduced surface modulus of at least about 20%, preferably at least about25%, more preferably at least about 30%, even more preferably at leastabout 35%, most preferably at least about 40%, relative to the innerlayer.

In any one of the preferred embodiments described above of the variousaspects of the invention, a contact lens produced according to a processof the invention has a friction rating of about 2 or lower (preferablyabout 1.5 or lower, more preferably about 1.0 or lower, even morepreferably about 0.5 or lower) after 30 cycles of digital rubbingtreatment.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. As would be obvious to one skilled in theart, many variations and modifications of the invention may be made bythose skilled in the art without departing from the spirit and scope ofthe novel concepts of the disclosure. In addition, it should beunderstood that aspects of the various embodiments of the invention maybe interchanged either in whole or in part or can be combined in anymanner and/or used together, as illustrated below:

-   1. A process for producing a contact lens, comprising the steps of:    -   (a) obtaining a contact lens precursor which is a coated contact        lens which comprises a lens bulk material completely covered        with an anchor layer of a polyanionic polymer which comprises at        least 60% by mole of repeating units of at least one        carboxyl-containing vinylic monomer; and    -   (b) heating, in the presence of at least one first polyaziridine        which has a number average molecular weight of about 2000 Dalton        or less and at least two aziridine groups, the contact lens        precursor in a first aqueous solution which comprises a        thermally-crosslinkable hydrophilic polymeric material which has        thermally-crosslinkable groups, to and at a temperature from        about 30° C. to about 140° C. for a period of time sufficient to        obtain the contact lens,    -   wherein the contact lens comprise (i) a crosslink anchor layer        thereon and (2) an outer surface hydrogel layer which is        covalently attached to the crosslinked anchor layer, wherein the        crosslinked anchor layer is obtained crosslinking the        polyanionic polymer in the anchor layer via crosslinkers derived        from said at least one polyaziridine in coupling reaction        between at least two pair of aziridine and carboxyl groups,        wherein the outer surface hydrogel layer is formed by        crosslinking the thermally-crosslinked hydrophilic polymeric        material, wherein the contact lens has a polyquaternium-1 uptake        (“PU_(pz)”) of about 0.6 μg/lens or less.-   2. The process of embodiment 1, wherein the contact lens has a    polyquaternium-1 uptake (“PU_(pz)”) of about 0.5 μg/lens or less.-   3. The process of embodiment 1, wherein the contact lens has a    polyquaternium-1 uptake (“PU_(pz)”) of about 0.4 μg/lens or less.-   4. The process of embodiment 1, wherein the contact lens has a    polyquaternium-1 uptake (“PU_(pz)”) of about 0.3 μg/lens or less.-   5. The process of embodiment 1, wherein the contact lens has a    polyquaternium-1 uptake (“PU_(pz)”) of about 0.2 μg/lens or less.-   6. The process of embodiment 1, wherein the contact lens has a    polyquaternium-1 uptake (“PU_(pz)”) of about 0.1 μg/lens or less.-   7. The process according to any one of embodiments 1 to 6, further    comprising a step of soaking the contact lens precursor in a second    aqueous solution comprising at least one second polyaziridine having    a number average molecular weight of about 2000 Dalton or less and    at least two aziridine groups.-   8. The process according to any one of embodiments 1 to 7, wherein    the first and second polyaziridine independent of each other have a    number average molecular weight of from 250 Daltons to 1500 Daltons.-   9. The process according to any one of embodiments 1 to 7, wherein    the first and second polyaziridine independent of each other have a    number average molecular weight of from 300 Dalton to 1000 Dalton.-   10. The process according to any one of embodiments 1 to 7, wherein    the first and second polyaziridine independent of each other have a    number average molecular weight of from 350 Dalton to about 800    Daltons.-   11. The process according to any one of embodiments 1 to 10, wherein    the first aqueous solution further comprises said at least one first    polyaziridine.-   12. The process of any one of embodiments 1 to 11, wherein the first    and second polyaziridines independent of each other are selected    from a group consisting of trimethylolpropane    tris(2-methyl-1-aziridinepropionate), pentaerythritol    tris[3-(1-aziridinyl)propionate], trimethylolpropane    tris(3-azindinopropionate), a Michael reaction product of a vinylic    crosslinker having at least three (meth)acryloyl groups and    2-methylaziridine, a Michael reaction product of a vinylic    crosslinker having at least three (meth)acryloyl groups and    aziridine, or a combination thereof.-   13. The process of embodiment 12, wherein the vinylic crosslinker is    selected from the group consisting of trimethylolpropane    triacrylate, pentaerythritol triacrylate,    tris(2-hydroxyethyl)isocyanurate triacrylate, trimethylolpropane    ethoxylate triacrylates, glyceryl propoxylate triacrylate,    trimethylolpropane propoxylate triacrylates, pentaerythritol    tetraacrylate, ditrimethylolpropane tetraacrylate, pentaerythritol    ethoxylate tetraacrylate, dipentaerythritol pentaacrylate,    caprolactone modified dipentaerythritol hexaacrylates, caprolactone    modified dipentaerythritol pentaacrylate, ethoxylated glycerol    triacrylate, ethoxylated trimethylolpropane trimethacrylate,    propoxylated trimethylolpropane trimethacrylate, ethoxylated    pentaerythritol trimethacrylate, ethoxylated pentaerythritol    tetramethacrylate, ethoxylated dipentaerythritol trimethacrylate,    ethoxylated dipentaerythritol tetramethacrylate, ethoxylated    dipentaerythritol pentamethacrylate, ethoxylated dipentaerythritol    hexamethacrylate, ethoxylated dipentaerythritol triacrylate,    ethoxylated dipentaerythritol tetraacrylate, ethoxylated    dipentaerythritol pentaacrylate, ethoxylated dipentaerythritol    hexaacrylate, propoxylated pentaerythritol trimethacrylate,    propoxylated pentaerythritol triacrylate, propoxylated    pentaerythritol tetramethacrylate, propoxylated pentaerythritol    tetraacrylate, propoxylated dipentaerythritol trimethacrylate,    propoxylated dipentaerythritol tetramethacrylate, propoxylated    dipentaerythritol pentamethacrylate, propoxylated dipentaerythritol    hexamethacrylate, propoxylated dipentaerythritol triacrylate,    propoxylated dipentaerythritol tetraacrylate, propoxylated    dipentaerythritol pentaacrylate and propoxylated dipentaerythritol    hexaacrylate, ethoxylated trimethyloylpropane triacrylamide, and    combinations thereof.-   14. The process of embodiment 12 or 13, wherein the first and second    aqueous solutions independent of each other comprise two    polyaziridines, a first polyaziridine having at least two aziridine    groups of

and a second polyaziridine having at least two aziridine groups of

and at least one hydrophilic moiety selected from the group consistingof —OH, —[OC₂H₄O]_(n1)—. —CONHR¹, —CONR¹—, and combinations thereof,wherein n1 is an integer of 1 to 10 and R¹ is hydrogen, methyl or ethyl.

-   15. The process of any one of embodiments 1 to 14, wherein the first    and second aqueous solutions independent of each other comprise from    about 0.01% to about 2.5% by weight of said at least one first or    second polyaziridine.-   16. The process of any one of embodiments 1 to 14, wherein the first    and second aqueous solutions independent of each other comprise from    about 0.02% to about 2.0% by weight of said at least one first or    second polyaziridine.-   17. The process of any one of embodiments 1 to 14, wherein the first    and second aqueous solutions independent of each other comprise from    about 0.05% to about 1.0% by weight of said at least one first or    second polyaziridine.-   18. The process of any one of embodiments 1 to 14, wherein the first    and second aqueous solutions independent of each other comprise from    about 0.05% to about 0.5% by weight of said at least one first or    second polyaziridine.-   19. The process of any one of embodiments 1 to 18, wherein the first    aqueous solution is a lens packaging solution, wherein the step of    heating is performed by autoclaving the contact lens precursor    immersed in the lens packaging solution in a sealed lens package at    a temperature of from about 115° C. to about 125° C. for    approximately 20-90 minutes.-   20. The process of embodiment 19, wherein the lens packaging    solution further comprises a partially hydrolyzed polyvinyl alcohol    having a hydrolysis degree of hydrolysis of from about 80% to about    98%.-   21. The process of embodiment 19 or 20, wherein the lens packaging    solution has a pH of from about 7.0 to about 9.0 before autoclaving    and a pH of from about 6.5 to about 7.7 after autoclaving.-   22. The process of any one of embodiments 19 to 21, wherein the    first aqueous solution is obtained directly in the lens package by    mixing a third aqueous solution and a fourth aqueous, wherein the    third aqueous solution comprises the thermally-crosslinkable    hydrophilic polymeric material.-   23. The process of embodiment 22, wherein the third aqueous solution    is free of any polyaziridine.-   24. The process of embodiment 22, wherein the third aqueous solution    further comprises said at least one polyaziridine.-   25. The process of any one of embodiments 22 to 24, wherein the    fourth aqueous solution comprises said at least one first    polyaziridine.-   26. The process of any one of embodiments 22 to 24, wherein the    fourth aqueous solution is free of any polyaziridine.-   27. The process of any one of embodiments 1 to 26, wherein said at    least one carboxyl-containing vinylic monomer is acrylic acid,    methacrylic acid, ethylacrylic acid, 2-(meth)acrylamidoglycolic    acid, and combinations thereof.-   28. The process of any one of embodiments 1 to 26, wherein the    polyanionic polymer is polyacrylic acid, polymethacrylic acid,    poly(ethylacrylic acid), poly(acrylic acid-co-methacrylic acid),    poly[ethylacrylic acid-co-(meth)acrylic acid],    poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylic    acid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone],    poly[ethylacrylic acid-co-acrylamide], poly[ethylacrylic    acid-co-vinylpyrrolidone], poly[(meth)acrylic acid-co-vinylacetate],    poly[ethylacrylic acid-co-vinylacetate], or combinations thereof.-   29. The process of any one of embodiments 1 to 26, wherein the    polyanionic polymer is a graft polymer which is grafted onto the    inner layer or the lens bulk material, wherein the graft polymer    comprises repeating units of at least one carboxyl-containing    vinylic monomer which is acrylic acid, methacrylic acid,    ethylacrylic acid, 2-(meth)acrylamidoglycolic acid, and combinations    thereof.-   30. The process of any one of embodiments 1 to 29, wherein the    thermally-crosslinkable hydrophilic polymeric material is a    partially-crosslinked polymeric material that comprises a    three-dimensional network and thermally-crosslinkable groups within    the network or being attached to the network.-   31. The process of embodiment 30, wherein the    thermally-crosslinkable hydrophilic polymeric material comprises    azetidinium groups and is a partial reaction product of at least one    azetidinium-containing polymer with at least one    hydrophilicity-enhancing agent having at least one carboxyl, primary    amine, secondary amine, or thiol group.-   32. The process of embodiment 30 or 31, wherein the    thermally-crosslinkable hydrophilic polymeric material comprises:    -   (i) from about 20% to about 95% by weight of first polymer        chains derived from at least one azetidinium-containing polymer,    -   (ii) from about 5% to about 80% by weight of hydrophilic        moieties each from at least one hydrophilicity-enhancing agent        having at least one reactive functional group selected from the        group consisting of amino group, carboxyl group, thiol group,        and combination thereof (preferably carboxyl groups), wherein        the hydrophilic moieties are covalently attached to the first        polymer chains through one or more covalent linkages each formed        between one azetidinium group of the azetidinium-containing        polymer and one amino, carboxyl or thiol group of the        hydrophilicity-enhancing agent, and    -   (iii) azetidinium groups which are parts of the first polymer        chains or pendant or terminal groups covalently attached to the        first polymer chains.-   33. The process of embodiment 30 or 31, wherein the    thermally-crosslinkable hydrophilic polymeric material comprises:    -   (i) from about 20% to about 95% by weight of first polymer        chains derived from at least one azetidinium-containing polymer,    -   (ii) from about 5% to about 80% by weight of second polymer        chains derived from at least one hydrophilicity-enhancing agent        having at least one reactive functional group selected from the        group consisting of amino group, carboxyl group, thiol group,        and combination thereof (preferably carboxyl groups), wherein        the second polymer chains are covalently attached to the first        polymer chains through one or more covalent linkages each formed        between one azetidinium group of the azetidinium-containing        polymer and one amino, carboxyl or thiol group of the        hydrophilicity-enhancing agent, and    -   (iii) azetidinium groups which are parts of the first polymer        chains or pendant or terminal groups covalently attached to the        first polymer chains.-   34. The process of embodiment 33 or 34, wherein said at least one    azetidinium-containing polymer is a polyamidoamine-epichlorohydrin.-   35. The process of embodiment 33 or 34, wherein said at least one    azetidinium-containing polymer is    poly(2-oxazoline-co-ethyleneimine)-epichlorohydrin.-   36. The process of any one of embodiments 31, 32, 34 and 35, wherein    the hydrophilicity-enhancing agent is a primary amine-containing    monosaccharide, a secondary amine-containing monosaccharide, a    carboxyl-containing monosaccharide, a thiol-containing    monosaccharide, a primary amine-containing disaccharide, a secondary    amine-containing disaccharide, a carboxyl-containing disaccharide, a    thiol-containing disaccharide, a primary amine-containing    oligosaccharide, a secondary amine-containing oligosaccharide, a    carboxyl-containing oligosaccharide, a thiol-containing    oligosaccharide, or a combination thereof.-   37. The process of any one of embodiments 31 and 33 to 35, wherein    the hydrophilicity-enhancing agent is: a polyethylene glycol having    one sole amino, carboxyl or thiol group; a polyethylene glycol with    two terminal amino, carboxyl and/or thiol groups; a multi-arm    polyethylene glycol with one or more amino, carboxyl and/or thiol    groups; a polyethylene glycol dendrimer with one or more amino,    carboxyl and/or thiol groups.-   38. The process of any one of embodiments 31 and 33 to 35, wherein    the hydrophilicity-enhancing agent is a copolymer which is a    polymerization product of a composition comprising (1) about 60% or    less by weight of one or more reactive vinylic monomers and (2) one    or more non-reactive hydrophilic vinylic monomers.-   39. The process of embodiment 38, wherein said one or more reactive    vinylic monomers are vinylic monomers having a carboxyl group    (preferably are selected from the group consisting of acrylic acid,    methacrylic acid, ethyl acrylic acid, N,N-2-acrylamidoglycolic acid,    and combinations thereof).-   40. The process of embodiment 38, wherein said one or more reactive    vinylic monomers are vinylic monomers having an amino group    (preferably are amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆    alkylamino-C₂-C₆ alkyl (meth)acrylate, allylamine, vinylamine,    amino-C₂-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl    (meth)acrylamide, and combinations thereof).-   41. The process of any one of embodiments 38 to 40, wherein said one    or more non-reactive vinylic monomers are selected from the group    consisting of (meth)acrylamide, N,N-dimethyl (meth)acrylamide,    N-vinylpyrrolidone (NVP), N-vinyl formamide, N-vinyl acetamide,    N-vinyl isopropylamide, N-vinyl-N-methyl acetamide,    N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl    (meth)acrylamide, glycerol (meth)acrylate,    3-(meth)acryloylamino-1-propanol, N-hydroxyethyl (meth)acrylamide,    N-hydroxypropyl (meth)acrylamide,    N-[tris(hydroxymethyl)methyl]-acrylamide,    N-methyl-3-methylene-2-pyrrolidone,    1-ethyl-3-methylene-2-pyrrolidone,    1-methyl-5-methylene-2-pyrrolidone,    1-ethyl-5-methylene-2-pyrrolidone,    5-methyl-3-methylene-2-pyrrolidone,    5-ethyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl (meth)acrylate,    hydroxypropyl (meth)acrylate, C₁-C₄-alkoxy polyethylene glycol    (meth)acrylate having a weight average molecular weight of up to    1500 Daltons, allyl alcohol, vinyl alcohol, and combinations thereof    (preferably from the group consisting of acryamide,    N,N-dimethylacrylamide, N-vinylpyrrolidone, (meth)acryloyloxyethyl    phosphorylcholine, N-vinyl-N-methyl acetamide, glycerol    (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl    (meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate    having a weight average molecular weight of up to 400 Daltons, vinyl    alcohol, and combination thereof).-   42. The process of any one of embodiments 38 to 40, wherein said one    or more non-reactive vinylic monomers are    phosphorylcholine-containing vinylic monomers (preferably    methacryloyloxyethyl phosphorylcholine).-   43. The process of any one of embodiments 38 to 42, wherein the    composition comprises about 50% or less by weight (preferably from    about 0.1% to about 30% by weight, more preferably from about 0.5%    to about 20% by weight, even more preferably from about 1% to about    15% by weight) of said one or more reactive vinylic monomers.-   44. The process of any one of embodiments 31 and 33 to 35, wherein    the hydrophilicity-enhancing agent is a primary amine-containing    polysaccharide, a secondary amine-containing polysaccharide, a    carboxyl-containing polysaccharide, hyaluronic acid, chondroitin    sulfate, or a combination thereof.-   45. The process of any one of embodiments 1 to 44, wherein the lens    bulk material is a silicone hydrogel material.-   46. The process of embodiment 45, wherein the silicone hydrogel bulk    material comprises: (1) repeating units of at least one polysiloxane    vinylic monomer; (2) repeating units of at least one hydrophilic    vinylic monomer; (3) repeating units of at least one polysiloxane    vinylic crosslinker; (4) repeating units of at least one hydrophilic    N-vinyl amide monomer; (5) repeating units of at least one    polycarbosiloxane vinylic monomer; (6) repeating units of at least    one polycarbosiloxane vinylic crosslinker; (7) repeating units of at    least one silicone-containing vinylic monomer having a    bis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl    group; (8) repeating units of one or more blending vinylic    monomers; (9) repeating units of one or more non-silicone vinylic    crosslinking agents; or (10) combinations thereof.-   47. The process of any one of embodiments 1 to 44, wherein the lens    bulk material is a non-silicone hydrogel material.-   48. The process of any one of embodiments 1 to 44, wherein the lens    bulk material comprise a central circular portion composed of a    rigid gas permeable lens material and an annular portion composed of    a non-silicone hydrogel material surrounding the central circular    portion.-   49. The process of embodiment 47 or 48, wherein the non-silicone    hydrogel material comprises repeating units of at least one    hydroxyl-containing vinylic monomer, wherein said at least one    hydroxyl-containing vinylic monomer is selected from the group    consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate,    3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate,    3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl    (meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide,    N-2-hydroxypropyl (meth)acrylamide, N-2,3-dihydroxypropyl    (meth)acrylamide, N-tris(hydroxymethyl)methyl (meth)acrylamide,    vinyl alcohol, allyl alcohol, and combinations thereof.-   50. The process of embodiment 47 or 48, wherein said at least one    hydroxyl-containing vinylic monomer is selected from the group    consisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate,    and vinyl alcohol.-   51. The process of any one of embodiments 1 to 44, wherein the lens    bulk material is a hard plastic material.-   52. The process of embodiment 51, wherein the hard plastic material    is a crosslinked polymethacrylate.-   53. The process of any one of embodiments 1 to 44, wherein the lens    bulk material is a rigid gas permeable lens material.-   54. The process of any one of embodiments 1 to 44, wherein the lens    bulk material is a crosslinked silicone material.-   55. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 10 seconds    after 30 cycles of digital rubbing treatment-   56. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 10 seconds    after simulated abrasion cycling treatment.-   57. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 15 seconds    after 30 cycles of digital rubbing treatment-   58. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 15 seconds    after simulated abrasion cycling treatment.-   59. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 20 seconds    after 30 cycles of digital rubbing treatment-   60. The process according to any one of embodiments 1 to 54, wherein    the contact lens has a water-break-up time of at least 20 seconds    after simulated abrasion cycling treatment.-   61. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 2.0 or lower after    30 cycles of digital rubbing treatment.-   62. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 2.0 or lower after    simulated abrasion cycling treatment-   63. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 1.5 or lower after    30 cycles of digital rubbing treatment.-   64. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 1.5 or lower after    simulated abrasion cycling treatment-   65. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 1.0 or lower after    30 cycles of digital rubbing treatment.-   66. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 1.0 or lower after    simulated abrasion cycling treatment-   67. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 0.5 or lower after    30 cycles of digital rubbing treatment.-   68. The process according to any one of embodiments 1 to 60, wherein    the contact lens has a friction rating of about 0.5 or lower after    simulated abrasion cycling treatment

The previous disclosure will enable one having ordinary skill in the artto practice the invention. Various modifications, variations, andcombinations can be made to the various embodiment described herein. Inorder to better enable the reader to understand specific embodiments andthe advantages thereof, reference to the following examples issuggested. It is intended that the specification and examples beconsidered as exemplary.

Example 1

Chemicals

The following abbreviations are used in the following examples: AMArepresents allyl methacrylate; NVP represents N-vinylpyrrolidone; DMArepresents N,N-dimethylacrylamide; VMA represents N-vinyl-N-methylacetamide; MMA represents methyl methacrylate; TEGDMA representtriethyleneglycol dimethacrylate; TEGDVE represents triethyleneglycoldivinyl ether; EGMA represents ethylene glycol methyl ethermethacrylate; VAZO 64 represents 2,2′-dimethyl-2,2′azodipropiononitrile;Nobloc is 2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylatefrom Aldrich; UV28 represents2-{2′-Hydroxy-3′-tert-butyl-5′-[3′-methacryloyloxypropoxy]phenyl}-5-chloro-2H-benzotriazole;RB246 is Reactive Blue 246; RB247 is Reactive Blue 247; TAA representstert-amyl alcohol; PrOH represents 1-propanol; IPA representsisopropanol; PAA represents polyacrylic acid; PMAA representspolymethacrylic acid; PAE represents polyamidoamine-epichlorohydrin(a.k.a., polyamine-epichlorohydrin); MPC represent2-methacryloyloxyethyl phosphorylcholine; Poly(AAm-co-AA) representspoly(acrylamide-co-acrylic acid); PZ-28 represents trimethylolpropanetris(2-methyl-1-aziridinepropionate); PZ-33 represents pentaerythritoltris[3-(1-aziridinyl)propionate]; BTP or Bis-TRIS-propane representbis[tris(hydroxymethyl)methylamino]propane; Tris-HCl representsTris(hydroxymethyl)aminomethane hydrochloride; EDTA representsethylenediaminetetraacetic acid; PBS represents a phosphate-bufferedsaline which has a pH of 7.2±0.2 at 25° C. and contains about 0.044 wt.% NaH₂PO₄.H₂O, about 0.388 wt. % Na₂HPO₄.2H₂O, and about 0.79 wt. % NaCland; wt. % represents weight percent; mSi1 representsmonobutyl-terminated monomethacryloxypropyl-terminatedpolydimethylsiloxane (Mw ˜600 to 800 g/mol from Gelest); D9 representsmonobutyl-terminated monomethacryloxypropyl-terminatedpolydimethylsiloxane (Mw ˜984 g/mol from Shin-Etsu); LM-CEPDMSrepresents a di-methacrylate-terminated chain-extendedpolydimethylsiloxane (Mn ˜6000 g/mol), which has threepolydimethylsiloxane (PDMS) segments linked via diurethane linkagesbetween two PDMS segments and two urethane linkages each located betweenone terminal methacrylate group and one PDMS segment, is preparedaccording to a method similar to what described in Example 2 of U.S.Pat. No. 8,529,057 (herein incorporated by reference in its entirety);“GA” macromer represents a di-methacryloyloxypropyl-terminatedpolysiloxane (Mn ˜6.8K g/mol, OH content ˜1.2 meq/g) of formula (A);“G4” macromer represents a di-methacryloyloxypropyl-terminatedpolysiloxane (Mn ˜13.5K g/mol, OH content ˜1.8 meq/g) of formula (A).

Oxygen Permeability Measurements

The apparent oxygen permeability (Dk_(app)), the apparent oxygentransmissibility (Dk/t), the intrinsic (or edge-corrected) oxygenpermeability (Dk_(c)) of a lens and a lens material are determinedaccording to procedures described in Example 1 of U.S. patentapplication publication No. 2012/0026457 A1 (herein incorporated byreference in its entirety).

Digital Rubbing Treatment

The lenses are digitally rubbed (wearing disposable powder-free latexgloves) with RENU® multi-purpose lens care solution (or anothermulti-purpose lens care solution) for 20 seconds and then rinsed withsaline. The above procedure is repeated for i time (i.e., i cycles ofdigital rubbing) that imitates daily cleaning in a i-days lens careregime, e.g. 7 times (i.e., 7 cycles of digital rubbing) that imitatesdaily cleaning and disinfecting in a 7-days lens care regime), or 30times (i.e., 30 cycles of digital rubbing) that imitates daily cleaningand disinfecting in a 30-days lens care regime.

Simulated Abrasion Cycling Treatment

To simulate a worst-case scenario for manual cycling, a simulatedabrasion technique is used to ensure consistent pressure and shearingconditions. To do this, a customized lens holder is made to grip thelens while shearing the lens. As shown in FIG. 3, the lens (part 1) isplaced on a rubber insert (part 2) with a 7.7 mm diameter central shaft(part 3) fitted axially. The top clip (part 4) is clipped onto thebottom clip (part 5), which holds the lens tightly against the siliconegasket. The central shaft is then extended so the lens is sticking abovethe outer body surface, exposing the lens circular area around thecenter of the lens. Optionally, a piece of cloth (i.e. Twillx 1622,Berkshire) can be placed between the central shaft and contact lens toenhance abrasion visualization.

The entire lens holder is placed on the attachment end of the Taberlinear abrader system (Taber Industries, model 5750,http://www.taberindustries.com/linear-abraser). With no added weightsare attached, the entire weight of the bearing arm and lens holder (230g normal force) is applied to the 47 mm² contact lens area, allowing 49kPa to be applied to the counter surface. For the counter surface, asheet of silicone rubber (10A, ¼ thick) is placed underneath the bearingarm, and a reservoir channel is clipped to the silicone rubber. Thereservoir is then filled with PBS at room temperature.

During the experiment, the lens holder is slowly dropped to the countersurface, and the lens is abraded 20 times (3″ per stroke, 6″ totaltravel per cycle) at a frequency of 75 cycles per minute. The lenssurface can be analyzed using the water break up time methodology,lubricity evaluation, and/or Sudan Black staining test.

While this technique applies a shear force well beyond what a typicalcontact lens would experience, this controlled shearing technique (i.e.,simulated abrasion cycling treatment) is found to be a reasonableequivalent of 30 cycles of digital rubbing treatment and providesassurance that these contact lenses will be able to handle even theharshest mechanical cycling.

Lubricity Evaluation.

The lubricity of a contact lens is evaluated by using a finger-feltlubricity test which characterizes qualitatively the slipperiness of alens surface on a friction rating scale of from 0 to 4. The higher thefriction rating is, the lower the slipperiness (or lubricity).

Commercial lenses: DAILIES® TOTAL1®; ACUVUE® OASYS™; ACUVUE® ADVANCEPLUS™; DAILIES® Aqua Comfort Plus®; and AIR OPTIX®, are assigned afriction rating (designated “FR” hereinafter) of 0, 1, 2, 3, and 4respectively. They are used as standard lenses for determining thefriction rating of a lens under test.

The samples are placed in PBS for at least two rinses of 30 minutes eachand then transferred to fresh PBS before the evaluation. Before theevaluation, hands are rinsed with a soap solution, extensively rinsedwith DI water and then dried with KimWipe® towels. The samples arehandled between the fingers and a numerical number is assigned for eachsample relative to the above standard lenses described above. Forexample, if lenses are determined to be only slightly better than AIROPTIX® lenses, then they are assigned a number 3. The value of afriction rating is one obtained by averaging the results of at least twofriction ratings of a contact lens by two or more persons and/or byaveraging the friction ratings of two or more contact lenses (from theidentical batch of lens production) by one person.

The finger lubricities (i.e., friction ratings) of a contact lens can bedetermined either directly out-of-pack (OOP) but after 230 min soakingin PBS) or after i cycles (e.g., 7, 14, 21, or 30 cycles) of digitalrubbing treatment, or after simulated abrasion cycling treatmentaccording to the procedures described above.

Surface Wettability Tests

Water contact angle (WCA) on a contact lens is a general measure of thesurface wettability of a contact lens. In particular, a low watercontact angle corresponds to more wettable surface. The dynamic captivebubble contact angles of contact lenses are measured using a FDSinstrument device from FDS Future Digital Scientific Corp. The FDSequipment is capable of measuring the advancing and receding contactangles. The measurement is performed on hydrated contact lenses at roomtemperature. A contact lens is removed from the vial and soaked in ˜40mL fresh PBS and shake for at least 30 minutes, then replace with freshPBS, soak and shake for another 30 minutes unless otherwise specified.The contact lens is then put on a lens paper and dabbed to removesurface water prior to be placed on top of a lens holder with frontcurve up then screw the lens holder top on. Place the secure lens holderinto the glass cell cuvette filled with filtered PBS. Place the glasscell cuvette onto the stage of the FDS instrument. Adjust the stageheight and the syringe needle to dispense the air bubble to the lenssurface. Repeat dispense/withdrawal 3 cycles for every lens to get theadvancing and receding contact angles. The receding contact angles arereported in the examples below.

Water Break-Up Time (WBUT) Tests

The surface hydrophilicity of lenses (after autoclave) is assessed bydetermining the time required for the water film to start breaking onthe lens surface. Lenses exhibiting WBUT ≥10 seconds are considered tohave a hydrophilic surface and are expected to exhibit adequatewettability (ability to support the tear film) on-eye.

Lenses are prepared for water breakup measurement by removing the lensfrom its blister with soft plastic tweezers (e.g., those from Menicon)and placing the lens in a test tube containing phosphate bufferedsaline. The test tube contains 10 mL phosphate buffered saline per lens,1 lens per test tube. Lenses are soaked overnight (at least 16 hours)before testing.

WBUT is measured at room temperature as follows: the lens is removedfrom the test tube and placed on a pedestal submerged in PBS. Thepedestal is then raised out of the PBS solution (t=0), and a videocamera monitors the fluid flowing off the lens surface. When the lenssurface fluid breaks, this WBUT time is recorded. Optionally, a stopwatch can be used to measure the time between when the pedestal israised out of the PBS and when the lens surface fluid breaks. Thepedestal is withdrawn, pulling the lens beneath the surface of the PBS.At least 3 spots per lenses are measured, and at least 3 lenses aremeasured to obtain an average WBUT measurement for each lens group.

Equilibrium Water Content

The equilibrium water content (EWC) of contact lenses is determined asfollows.

Amount of water (expressed as percent by weight) present in a hydratedhydrogel contact lens, which is fully equilibrated in saline solution,is determined at room temperature. Quickly stack the lenses, andtransfer the lens stack to the aluminum pan on the analytical balanceafter blotting lens in a cloth. The number of lenses for each sample panis typically five (5). Record the pan plus hydrated weight of thelenses. Cover the pan with aluminum foil. Place pans in a laboratoryoven at 100±2° C. to dry for 16-18 hours. Remove pan plus lenses fromthe oven and cool in a desiccator for at least 30 minutes. Remove asingle pan from the desiccator, and discard the aluminum foil. Weigh thepan plus dried lens sample on an analytical balance. Repeat for allpans. The wet and dry weight of the lens samples can be calculated bysubtracting the weight of the empty weigh pan.

Elastic Modulus

The elastic modulus of a contact lens is determined using a MTS insightinstrument. The contact lens is first cut into a 3.12 mm wide stripusing Precision Concept two stage cutter. Five thickness values aremeasured within 6.5 mm gauge length. The strip is mounted on theinstrument grips and submerged in PBS with the temperature controlled at21±2° C. Typically 5N Load cell is used for the test. Constant force andspeed is applied to the sample until the sample breaks. Force anddisplacement data are collected by the TestWorks software. The elasticmodulus value is calculated by the TestWorks software which is the slopeor tangent of the stress vs. strain curve near zero elongation, in theelastic deformation region.

Determinations of Polyquaternium-1 Uptakes (PU).

Polyquaternium-1 uptake by a contact lens is determined according to aDNA intercalation procedure based on a PicoGreen dsDNA assay kit (i.e.Quanti-iT PicoGreen dsDNA kit, ThermoFisher). Polyquatemium-1 uptake bya contact lens is determined as follows:

A basis solution is prepared by dissolving the following components inpurified water 5 ppm myristamidopropyldimethylamine; 1000 ppm sodiumdecanoyl ethylenediamine triacetate; 83 ppm sodium citrate dehydrate;1000 ppm NaCl; 1000 ppm Tetronic 1304; 1150 ppm sodium boratedecahydrate; and 10000 ppm propylene glycol and then by adjusting pH toabout 7.8.

The Polyquaternium-1 (PQ) testing solution is prepared by dissolving adesired amount in the basis solution prepared above to have 5 ppm PQ andthen by adjusting pH to about 7.8 if necessary. A series of PQ standardsolutions each having a concentration within a range are prepared toestablish a calibration curve between 0 and 6 ppm (or higher) of PQ.

Contact lenses are removed from their individual lens packages andshaken in 25 ml PBS per lens for 30 minutes. The PBS-soaked lenses areblotted with a paper towel (preferably with W4 polypropylene towels fromKimberly Clark) with a fixed weight (i.e. 0.6 kg) before being incubatedovernight.

A 24-well plate will be used in the overnight incubation experiment. Thewells are divided into the following categories: negative-control wellseach containing 0.5 mL of the basis solution and two blotted contactlenses fully immersed therein; positive-control wells each containing0.5 mL of the polyquaternium-1 testing solution; samples wells eachcontaining 0.5 mL of the polyquaternium-1 testing solution and twoblotted contact lenses fully immersed therein; standard wells eachcontaining 0.5 mL of one of one of the standard solutions. The 24-wellplate then is shaken for 20 minutes on an orbital shaker and then sitson a bench top overnight (for 16-20 hours) at room temperature.

A 25 μL aliquot from each of the wells of the overnight incubated24-well plate is added to a 96-well plate (e.g. DNA LoBind, Eppendorf)cell well containing 450 μL of a Lambda DNA solution (1 μg/mL LambdaDNA; 10 mM Tris-HCl; 1 mM EDTA; pH 7.5). The solution is mixed andincubated on an orbital shaker at 700-800 rpm for 60 minutes.

A 100 μL aliquot from each of the DNA-incubated cell wells aretransferred to a 96-well plate (e.g., black opaque, med bind, Grenier).Then 100 μL of the PicoGreen solution (ThermoFisher, diluted withTris-EDTA buffer [10 mM Tris-HCl, 1 mM EDTA, pH 7.5] per kitinstructions) are added to each of those wells and mixed. The cell wellsare then incubated on an orbital shaker for 5 minutes at 250 rpm. Eachplate is read with a fluorescence plate reader (e.g., Victor X5 PlateReader, Perkin Elmer) using standard fluorescence excitation andemission wavelengths for the PicoGreen. Each sample is compared againstthe linear fit of the standard curve to obtain final PQ concentration ineach solution. The amount of PQ uptake per lens is obtained bymultiplying the incubation volume and dividing by the number of lensesincubated. The PQ uptake by the lens is calculated to be the differencein [polyquaternium-1] between the DNA-incubated positive-control andsample solutions, times the incubation volume (0.5 mL) and divide by 2.

Surface Cracking (SC) Tests

Tests for evaluating surface cracking are carried out as follows. Removelens from the package. Invert the lens inside-out gently (i.e.,rendering the lens in the invert form) by holding the edge of the lensbetween the thumb and index finger of one hand. The concave side of thelens should face the experimenter's body. With the thumb and/or indexfinger of the other hand, gently bend the top of the lens over the indexfinger holding the lens until the lens confirmation inverts. Followingthat, fold the lens gently in half and apply slight pressure to thefolded lens. Afterward, revert the lens to its original form prior tothe lens inversion and repeat the aforementioned steps. Place the lensin a Petri dish and inspect lens using a darkfield stereomicroscope.Lens surface cracking is first inspected at low magnification (i.e.,10-20×) with focus on the center of the lens, if crack lines are notdistinguishable, lens is further inspected at high magnification (e.g.,35-45×). If no cracking is observed in 45× magnifications, lens receivesa surface cracking rating of zero (0). If cracking is observed, thecracking rating is accomplished by counting the number of split lines:rating of 1=2-4 lines in field-of-view; rating of 2=5-8 lines; rating of3≥8 lines.

Coating Intactness Tests

The intactness of a coating on the surface of a contact lens can betested according to Sudan Black stain test as follow. Contact lenseswith a coating (an LbL coating, a plasma coating, a hydrogel coating, orany other coatings) are dipped into a Sudan Black dye solution (SudanBlack in the mixture ˜80% mineral oil and ˜20% vitamin E oil). SudanBlack dye is hydrophobic and has a great tendency to be adsorbed by ahydrophobic material or onto a hydrophobic lens surface or hydrophobicspots on a partially coated surface of a hydrophobic lens (e.g.,silicone hydrogel contact lens). If the coating on a hydrophobic lens isintact, no staining spots should be observed on or in the lens. All ofthe lenses under test are fully hydrated. Visible fine lines on lenssurface may indicate the presence of cracking of the crosslinkedcoatings.

Comparative Example

The approaches disclosed in US2016/0326046 A1 (herein incorporated byreference in its entirety) are used in this example to reduce uptakes ofpositively-charged antimicrobials by water gradient contact lenses.

PMAA-Coating Solution.

A polymethacrylic acid (PMAA) coating solution is prepared by dissolvingan amount of PMAA (Mn: 300-600 kDa, from Polysciences, Inc.) in a givenvolume of 1-propanol/water (90%/10% wt/wt) mixture to have aconcentration of about 0.011% by weight and the pH is adjusted withformic acid to about 2.0.

PAE Sol-1.

A PAE solution is prepared by dissolving an amount of polyamidoamineepichlorohydrin (Kymene) in a given volume of water to have aconcentration of about 0.5% by weight and the pH is adjusted to adesired pH (e.g., 2.0, 3.5, 7, or 9).

PAE Sol-2.

A PAE solution is prepared by dissolving an amount of polyamidoamineepichlorohydrin (Kymene) in a given volume of a mixture of water (68% byweight) and 1-propanol (32% by weight) to have a concentration of about0.5% by weight and the pH is adjusted to pH 2.0.

Preparation of In-Package-Coating (IPC) Saline—IPC-1

A MPC-containing copolymer (Mw 230-320 kD) comprising about 90 mole % of2-methacryloyloxyethyl phosphorylcholine (MPC) and about 10 mole % of

in which X is a monovalent radical of —CH₂CH(OH)CH₂SCH₂CH₂N H₂ or—CH₂CH(CH₂OH)SCH₂CH₂NH₂ is prepared according to procedures similar tothose described in Example 1-2 of U.S. Pat. No. 9,127,099B2 (hereinincorporated by reference in its entirety). The MPC-containing copolymerused is an aqueous solution with solid content ˜10 wt % of theMPC-containing copolymer.

PAE solutions (Kymene) are purchased from Ashland as an aqueous solutionand used as received.

IPC-1 saline is prepared as follows. Mix about 74 wt % of theMPC-containing copolymer solution, about 6 wt % PAE solution, and about20 wt % of a phosphate buffer (about 0.22 wt % NaH₂PO₄.H₂O, 1.95 wt %Na₂HPO₄.2H₂O, and about 4 wt % NaCl) (the concentration of theMPC-containing copolymer and PAE are about 10 times of the finalsaline). Adjust pH to ˜7.3 by 1N NaOH. React the mixture in a water bathat temperature=70° C. for 4 hours to form water-solublethermally-crosslinkable polymeric material (i.e.,“in-package-crosslinking agent) or “IPC agent”). Remove the mixture fromwater bath and cool down in a room temperature water bath. Dilute themixture 10 times with PBS and adjust pH to ˜7.3. Filter the mixture by0.22 μm PES sterile filter unit.

Cast-Molded Silicone Hydrogel (SiHy) Contact Lenses.

SiHy contact lenses (uncoated) are cast-molded according to theprocedures described in Example 3 of US2016/0326046 A1.

Application of Crosslinked Coating.

The cast-molded SiHy contact lenses are extracted and coated by dippingin a series of baths: 1^(st)-3^(rd) baths—3 MEK baths (about 22 seconds,about 138 seconds and about 224 seconds respectively); 4^(th) bath—DIwater bath (about 56 seconds); 5^(th)-7^(th) baths—shown in Table 1;8^(th) bath—DI water (about 56 seconds unless indicated otherwise);9^(th)—DI water (about 56 seconds); 10^(th) baths—DI water (about 168seconds). All the bath temperatures are at room temperature (i.e., about22-26° C.) unless indicated otherwise. After the 10^(th) bath, thecontact lenses are individually packaged in polypropylene lens packagingshells (blisters) with 0.6 mL of IPC-1 saline (half of the IPC-1 salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at 121° C., forming crosslinkedcoatings on the lenses.

TABLE 1 Lens Bath 5 Bath 6 Bath 7 Sam- time time time ple [PMAA] (s)solution (s) Solution (s) T1 200 ppm 44 PBS 56 PAE Sol-1 (pH 2.0) 300 T2200 ppm 44 PBS 56 PAE Sol-1 (pH 7.0) 300 T3 200 ppm 44 PBS 56 PAE Sol-1(pH 9.0) 300 T4 133 ppm 44 PBS 56 PAE Sol-1 (pH 2.0) 300 T5 200 ppm 44PAE Sol-2 300 DI water 56 T6 133 ppm 44 PAE Sol-2 56 DI water 56 T7 133ppm 44 PAE Sol-2 300 DI water 56 T8^(a) 200 ppm 44 PBS 56 DI water 300T9^(a) 200 ppm 120 PBS 56 DI water 300 T10 mixture^(b) 44 PBS 56 DIwater 300 C1 200 ppm 44 DI water 56 DI water 56 C2 200 ppm 44PrOH:H₂O^(c) 56 DI water 56 C3^(a) 133 ppm 44 DI water 56 DI water 56C4^(a) 200 ppm 120 DI water 56 DI water 56 C5 133 ppm 44 DI water 56 DIwater 56 C6 133 ppm 44 PrOH:H₂O^(c) 56 DI water 56 ^(a)The temperatureof the 8^(th) bath is about 80° C. and the dipping time is about 30minutes; ^(b)a solution containing 200 ppm of PMAA and 0.5% by weight ofPAE (pH ~2); ^(c)mixture of PrOH and DI water at a weight ratio of 68/32(pH 2.0).

Then the lenses are tested for the amount of carboxyl groups per lensaccording to the procedure described in Example 2 of US2016/0326046A1(herein incorporated by reference in its entirety), and also aresubjected to digital rubbing tests and evaluated for lubricity (frictionrating) according to the procedures described in Example 1.

Control lenses (C3 and C4) and testing lenses (T8 and T9) have alubricity of 4 directly out of packages and were not subjecting tocycling-lubricity tests. Such results may indicate that heating thelenses with PMAA coating thereon could lead to lose PMMA sosignificantly that there is an insufficient amount of PMAA left on thelens for reacting with the thermally-crosslinkable material to form ahydrogel top coating.

Testing lenses (T2 and T3) have a lubricity of 3 and 4 respectivelydirectly out of packages. Such results may indicate that at a higher pH(7 or 9), PMAA is charged and PAE cannot penetrate into the PMAA coatingbut forms a layer on top of the PMAA coating. The top layer of PAE wouldprevent the underneath PMAA from reacting with thethermally-crosslinkable polymeric material to form a hydrogel topcoating. During autoclave, the top layer of PAE would be crosslinkedwith the PMAA coating to form a crosslinked coating with inferiorlubricity.

The results in Table 2 in indicate that the approaches disclosed inUS2016/0326046A1 may not be sufficient to produce water gradient contactlens with inadequate lubricity after cycled with Renu lens care solutionand no noticeable reduction in uptake of positively-chargedantimicrobials.

TABLE 2 Lubricity [COOH] Lens Sample 0X 7X 14X 30X (nmole/lens) C1 0 02.2 4 C2 0 0 3.4 4 C5 0 0.3 2 4 12.0 C6 0 0.4 2 4 12.4 T1 0 0 0.5 2.1 T40 0 0.8 2.6 13.7 T5 0 0 0.3 2.2 T6 0 0 2 3.6 T7 0 0 1 3.2 12.6 T10 0 3 44

Example 2

Preparation of Polymerizable Compositions

Lens formulations (polymerizable compositions), III to VI, are preparedto have compositions (in unit parts) as shown in Table 3.

TABLE 3 Formula- Formula- Formula- Formula- tion III tion IV tion V tionVI D9 33 33 33 33 G4 10 10 10 10 NVP 46 46 46 46 MMA 10 10 10 10 TEGDMA0.2 0.2 0.2 0.65 Norbloc 1.5 1.5 1.8 1.5 UV28 0.26 0.26 0 0.4 VAZO 640.5 0.5 0.5 0.5 RB247 0.01 0.01 0.01 0.01 TAA 10 10 10 10 Curing55/80/100° 55/80/100° 55/80/100° 55/80/100° Profile C. 30 min/2 C. 40min/40 C. 30 min/120 C. 30 min/120 hr/30 min min/40 min min/30 minmin/30 min

The formulations are prepared by adding listed components in theirtargeted amounts into a clean bottle, with a stir bar to mix at 600 rpmfor 30 minutes at room temperature. After all the solid is dissolved, afiltration of the formulation is carried out by using 2.7 μmglass-microfiber-filter.

Cast-Molded Silicone Hydrogel Contact Lenses

A lens formulation is purged with nitrogen at room temperature for 30 to35 minutes. The N₂-purged lens formulation is introduced intopolypropylene molds and thermally cured in an oven under the followingcuring conditions: ramping from room temperature to a first temperatureand then holding at the first temperature for a first curing timeperiod; ramping from the first temperature to a second temperature andholding at the second temperature for a second curing time period;optionally ramping from the second temperature to a third temperatureand holding at the third temperature for a third curing time period; andoptionally ramping from the third temperature to a fourth temperatureand holding at the fourth temperature for a fourth curing time period.

Lens molds are opened by using a demolding machine with a push pin.Lenses are pushed onto base curve molds with a push pin and then moldsare separated into base curve mold halves and front curve mold halves.The base curve mold halves with a lens thereon are placed in anultrasonic device (e.g., Dukane's single horn ultrasonic device). With acertain energy force, a dry state lens is released from mold. The drystate lens is loaded in a designed extraction tray. Alternatively,lenses can be removed from the base curve mold halves by floating off(i.e., soaking in an organic solvent, e.g., IPA, without ultrasonic).

The obtained silicone hydrogel (SiHy) contact lenses are subjected tothe following post-molding processes before lens characterization. Afterdemolding, SiHy lenses prepared above are extracted with 100% IPA for 15minutes, immersed in 50%/50% IPA/water mixture for 30 minutes and thenin DI water for 30 minutes, and finally rinsed with PBS saline for about60 minutes at room temperature. After rinsing in PBS with 5 min, thelens then is placed in polypropylene lens packaging shells (or blisters)(one lens per shell) with 0.6 mL of PBS. The blisters are then sealedwith foil and autoclaved for about 45 minutes at about 121° C. Theresultant SiHy contact lenses are characterized according to theprocedures to have the following properties: Dkc ˜105 barrers-118barrers; EWC ˜54%-57%; elastic modulus ˜0.45 MPa-0.62 MPa; WBUT ˜23seconds-40 seconds; water contact angle by captive bubble ˜47°-52°, afriction rating of about 2.0.

Example 3

Preparation of PAA Aqueous Solution

An aqueous solution of polyacrylic acid (PAA) is prepared by addingadequate amount of PAA (Mn ˜450 KD) in water (distilled or deionizedwater). After PAA is fully dissolved, the pH is adjusted by adding˜1.85% formic acid to the PAA aqueous solution to about 2. The targetconcentration of PAA is about 0.1% by weight. The prepared PAA aqueoussolution is filtered to remove any particulate or foreign matter.

Phosphate Buffered Saline (PBS)

A phosphate buffered saline is prepared by dissolving NaH₂PO₄.H₂O,Na₂HPO₄.2H₂O, and in a given volume of purified water (distilled ordeionized) to have the following composition: ca. 0.044 w/w %NaH₂PO₄.H₂O, ca. 0.388 w/w/% Na₂HPO₄.2H₂O, and ca. 0.79 w/w % NaCl.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared using the same procedure for preparing PBS, but no NaClis added.

Example 4

Preparation of PAA Coating Solution

A PAA coating solution is prepared by adding adequate amount of PAA (Mn˜450 KD) in a 50/50 water-IPA mixtures. After PAA is fully dissolved,the pH is adjusted by adding ˜1.85% formic acid to the PAA aqueoussolution to about 2. The target concentration of PAA is about 0.1% byweight. The prepared PAA coating solution is filtered to remove anyparticulate or foreign matter.

Phosphate Buffered Saline (PBS)

A phosphate buffered saline is prepared by dissolving NaH₂PO₄.H₂O,Na₂HPO₄.2H₂O, and in a given volume of purified water (distilled ordeionized) to have the following composition: ca. 0.044 w/w %NaH₂PO4.H₂O, ca. 0.388 w/w/% Na₂HPO₄.2H₂O, and ca. 0.79 w/w % NaCl.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared using the same procedure for preparing PBS, but no NaClis added.

Preparation of Aqueous Polyaziridine Solution

PZ-28 solutions having a PZ-28 concentration of 0.125%, 0.25% or 0.5%are prepared by simply adding PZ-28 into DI water and adjusting the pHto about 7.4.

PU reduction by PZ of PAA-Coated SiHy Contact Lenses

After de-molding, dry SiHy contact lenses (prepared in Example 2) areextracted with isopropanol (IPA) for 180 minutes for lens extraction,dip-coated in the PAA solution prepared above for about 30 minutes,rinsed with PB twice each for about 15 minutes, and then are immersed ina PZ-28 solution prepared above at about 60° C. for about 2 hours. Afterthe PZ-28 dipping step, the lenses are again rinsed in PB twice (15minutes each) and then subjected to various testing as shown in Table 4.

TABLE 4 [PZ-28] (wt. %) in Friction PU Surface PZ-28 dipping step Rating(μg/lens) Cracking* None (control) 0 16.3 ± 0.1  0, 0, 0 0.5 4  0 ± 0.20, 0, 3 0.25 4  0.4 ± 0.01 0, 0, 3 0.125 4 0.9 ± 0.2 0, 0, faint*inspection results of three lenses after finger rubbing.

The results in Table 4 show that after the various PZ dip treatments thePolyquarternium-1 uptake by PAA-coated SiHy contact lenses can besignificantly reduced by PZ-28 due to the reaction between the aziridinegroups of PZ-28 and the —COOH groups in the PAA coating on the lenssurface at about 60° C. (a relatively high temperature). Even at aconcentration of about 0.125 wt %, PZ-28 can still significantly reducethe Polyquarternium-1 uptake (PU) by PAA-coated SiHy lenses, whileadversely affecting the lubricity.

Table 5 shows the results of the treatments of PAA-coated SiHy contactlenses by a 0.25 wt % PZ-28 at room temperature and 45° C. for about onehour, in order to evaluate the effects of PZ-28 dipping temperature uponPZ-28 potency in reducing PU. Table 5 shows that there is a significantimprovement in PZ-28 potency at 45° C. compared to performing the PZ dipat room temperature (RT). Polyquarternium-1 uptake reduction is around55% at room temperature when compared to around 93% when the dip wasperformed at 45° C. This shows that the PZ-28 potency is elevated athigher temperatures above RT.

TABLE 5 Temperature of PZ-28 Friction PU Surface solution in dippingstep Rating (μg/lens) Cracking* None (control) 0 16.1 ± 0.7  0, 0, 0 45°C. 4 1.1 ± 0.2 0, 0, 0 Room temperature 0 7.3 ± 0.3 0, 0, 0 *inspectionresults of three lenses after finger rubbing.

Example 5

Preparation of PMAA Solution

A polymethacrylic acid (PMAA) coating solution is prepared by dissolvingan amount of PMAA (Mn: 400-700 kDa, from PolyMaterials, Inc.) in a givenvolume of 1-propanol/water (25/75 volume ratio) mixture to have aconcentration of about 0.06% by weight and the pH is adjusted withformic acid (typically about 1.8 wt % in the final solution) to about2.0.

Phosphate Buffered Saline (PBS)

PBS is prepared according to the procedures described in Example 3.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

IPC Salines (IPC-2, IPC-3, IPC-4, IPC-5, and IPC-6)

A MPC-containing copolymer (Mw 230-320 kD) comprising about 90 mole % of2-methacryloyloxyethyl phosphorylcholine (MPC) and about 10 mole % of

in which X is a monovalent radical of —CH₂CH(OH)CH₂SCH₂CH₂NH₂ or—CH₂CH(CH₂OH)SCH₂CH₂NH₂ is prepared according to procedures similar tothose described in Example 1-2 of U.S. Pat. No. 9,127,099B2 (hereinincorporated by reference in its entirety). The MPC-containing copolymerused is an aqueous solution with solid content ˜10 wt % of theMPC-containing copolymer.

PAE solutions (Kymene) are purchased from Ashland as an aqueous solutionand used as received.

The IPC-2 saline is prepared as follows. Mix about 74.3 wt % of theMPC-containing copolymer solution, about 3.7 wt % PAE solution, andabout 22 wt % of a phosphate buffer (about 0.22 wt % NaH₂PO₄.H₂O, 1.95wt % Na₂HPO₄.2H₂O, and about 4 wt % NaCl) (the concentration of theMPC-containing copolymer and PAE are about 10 times of the finalsaline). Adjust pH to ˜7.3 by 1N NaOH. React the mixture in a water bathat temperature=70° C. for 4 hours to form water-solublethermally-crosslinkable polymeric material (i.e.,“in-package-crosslinking agent) or “IPC agent”). Remove the mixture fromwater bath and cool down in a room temperature water bath. Dilute themixture 10 times with PBS and adjust pH to ˜7.3. Filter the mixture by0.22 μm PES sterile filter unit.

Four IPC salines (IPC-3 to IPC-6) having a concentration of 0.05 wt %.0.1 wt %, 0.5 wt % and 1 wt % of PZ-28 respectively are prepared byadding a desired amount of PZ-28 in IPC-2 saline and then by adjustingthe pH to 7.5. Up to 5 ppm hydrogen peroxide maybe added to each IPCsalines to prevent bioburden growth and each IPC saline is filteredusing a 0.22 micron membrane filter.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with isopropanol (IPA) for 180 minutes for lensextraction, dip-coated in the PMAA solution prepared above for about onehour, rinsed with PBS for about 60 minutes, and then are packaged/sealedin polypropylene lens packaging shells (blisters) with 0.6 mL of one ofIPC-2 to IPC-6 salines prepared above (half of the IPC saline is addedprior to inserting the lens). The sealed lens packages are autoclavedfor about 45 minutes at about 121° C., forming SiHy contact lenses witha cross-linked hydrophilic coating (i.e., a hydrogel coating) thereon.The coating uniformity or intactness is tested by Sudan black dyetesting and the coating passed Sudan black dye testing.

The resultant water gradient SiHy contact lenses is fairly lubricious(having a friction rating of about 0), a WBUT of more than 20 seconds,and water contact angle by static sessile drop of 40. They aredetermined to have a PU of 0.5, 0.19, 0.19, 0 and 0 respectively forwater gradient contact lenses prepared respectively from IPC-2 saline (0wt % PZ-28), IPC-3 saline (0.05 wt % PZ-28), IPC-4 saline (0.1 wt %PZ-28), IPC-5 saline (0.5 wt % PZ-28), and IPC-6 saline (1.0 wt %PZ-28).

Example 6

Preparation of PAA Coating Solution

A PAA coating solution is prepared by adding adequate amount of PAA (Mn˜450 KD) in a water-IPA mixture having water content shown in Table 6 tohave a desired PAA concentration shown in Table 6. After PAA is fullydissolved, the pH is adjusted by adding ˜1.85% formic acid to the PAAaqueous solution to about 2. The prepared PAA coating solution isfiltered to remove any particulate or foreign matter.

Phosphate Buffered Saline (PBS)

PBS is prepared according to the procedures described in Example 3.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

Preparation of Poly(MPC-co-AEM) (96/4 wt/wt)

A copolymer, poly(2-methacryloyloxyethylphosphorylcholine-co-2-Aminoethylmethacrylate)(96/4 w/w) (i.e.,poly(MPC-co-AEM), is prepared by thermal polymerizing a polymerizablecomposition comprising: about 96 wt % MPC; about 4 wt % AEM; about 0.02wt % Vazo 56 [2,2′-Azobis(2-methylpropionamidine) dihydrochloride];about 0.1 wt % chain transfer agent (HS—CH2CH2OH) in water at about 60°C. for about 2 hours and then at 20° C. for about 2 hours. The obtainedpoly(MPC-co-AEM) (an aqueous solution with solid content ˜10%) isdetermined to have an amine functionality of ˜0.22 meq/g, and a Mn of˜160 kDa.

The obtained copolymer is used as a hydrophilicity-enhancing agent forpreparing a water soluble thermally-crosslinkable polymeric material(i.e., “in-package-crosslinking agent” or “IPC agent”) in a reactionwith polyamidoamine-epichlorohydrin (PAE). PAE solutions (Kymene) arepurchased from Ashland as an aqueous solution and used as received.

IPC-7 Saline

The IPC-7 saline is prepared as follows. Mix 77 w/w % poly(MPC-co-AEM)aqueous solution prepared above, 6.1 w/w % PAE, and 16.9 w/w % of aphosphate buffer (about 128 mM of phosphate sodium salts and about 4 wt% NaCl) (the concentration of poly(MPC-co-AEM) and PAE are about 10times of the final saline). Adjust pH to ˜7.3 by 1N NaOH. React themixture in a water bath at temperature=70° C. for 3 hours. Remove themixture from water bath and cool down in a room temperature water bath.Dilute the mixture 10 times with a phosphate buffer (˜33 mM of phosphatesodium salts and 0.77 wt % NaCl) and adjust pH to ˜7.3. Filter themixture by 0.22 μm PES sterile filter unit.

IPC-8 Saline

IPC-8 saline is prepared by adding PZ-28 to IPC-7 saline to have a PZ-28concentration of 0.2 wt %. Up to 5 ppm hydrogen peroxide maybe added toeach IPC salines to prevent bioburden growth and each IPC saline isfiltered using a 0.22 micron membrane filter.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with isopropanol (IPA) for 180 minutes for lensextraction, dip-coated in the PAA solution prepared above for a timeperiod specified in Table 6, rinsed with PB twice each for about 30minutes, and then are packaged/sealed in polypropylene lens packagingshells (blisters) with 0.6 mL of either IPC-7 saline or IPC-8 salineprepared above (half of the IPC saline is added prior to inserting thelens). The sealed lens packages are autoclaved for about 45 minutes atabout 121° C., forming SiHy contact lenses with a cross-linkedhydrophilic coating (i.e., a hydrogel coating) thereon. The coatinguniformity or intactness is tested by Sudan black dye testing and thecoating passed Sudan black dye testing.

The resultant water gradient SiHy contact lenses is lubricious (having afriction rating of about 0), a WBUT of more than 20 seconds, and watercontact angle by static sessile drop of about 40 degrees. They aredetermined to have a PU shown in Table 6.

TABLE 6 PAA coating solution PU (μg/lens) [PAA] Water content Dippingtime IPC-7 IPC-8 (ppm) (wt %) (min) (free PZ-28) (0.2 wt % PZ-28) 250 7010 0.65 0.42 250 70 15 1.68 1.31 100 70 10 0.40 0.15 250 50 10 1.00 0.46100 50 6 0.23 0.00

Example 7

PMAA-Coating Solution

A polymethacrylic acid (PMAA) coating solution is prepared by dissolvingan amount of PMAA (Mn: 400-700 kDa, from PolyMaterials, Inc.) in a givenvolume of 1-propanol/water (49%/51% wt/wt) mixture to have aconcentration of about 0.06% by weight and the pH is adjusted withformic acid (typically about 1.8 wt % in the final solution) to about2.0.

Phosphate Buffered Saline (PBS)

PBS is prepared according to the procedures described in Example 3.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

Preparation of BTP Solutions

Bis-tris propane solution is prepared by dissolving BTP in DI (ordistilled) water to have a concentration of 300 ppm and then adjustingpH to 7.5.

Preparation of Aqueous Polyaziridine Solution

PZ-28 solutions having a PZ-28 concentration of 0.15% are prepared bysimply adding PZ-28 into the BTP solution prepared above and adjustingthe pH to about 7.4.

Preparation of Poly(MPC-co-AEM) (96/4 wt/wt)

Poly(2-methacryloyloxyethylphosphorylcholine-co-2-Aminoethylmethacrylate)(96/4 w/w) (i.e.,poly(MPC-co-AEM) is prepared according to the procedure described inExample 6.

IPC-9 Saline

IPC-9 saline is prepared as follows. Mix 77 w/w % poly(MPC-co-AEM)aqueous solution prepared above, 6.1 w/w % PAE, and 16.9 w/w % of aphosphate buffer (about 128 mM of phosphate sodium salts and about 4 wt% NaCl) (the concentration of poly(MPC-co-AEM) and PAE are about 10times of the final saline). Adjust pH to ˜7.3 by 1N NaOH. React themixture in a water bath at temperature=70° C. for 3 hours. Remove themixture from water bath and cool down in a room temperature water bath.Dilute the mixture 5 times with a phosphate buffer (˜33 mM of phosphatesodium salts and 0.77 wt % NaCl) and adjust pH to ˜7.3. Filter themixture by 0.22 μm PES sterile filter unit.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with isopropanol (IPA) for 180 minutes for lensextraction, dip-coated in the PMAA solution prepared above for about onehour, rinsed with PB twice each for about 30 minutes, and then arepackaged/sealed in polypropylene lens packaging shells (blisters) with0.6 mL of a mixture of PZ-28 solution and IPC-9 saline prepared above(0.3 mL of the PZ-28 solution is added prior to inserting the lens andthen 0.3 mL of IPC-9 is added and mixed). The sealed lens packages areautoclaved for about 45 minutes at about 121° C., forming SiHy contactlenses with a cross-linked hydrophilic coating (i.e., a hydrogelcoating) thereon. The coating uniformity or intactness is tested bySudan black dye testing and the coating passed Sudan black dye testing.

The resultant water gradient SiHy contact lenses is lubricious (having afriction rating of about 0) either directly out of package or aftersimulated abrasion cycling treatment (i.e., equivalent to 30 cycles ofdigital rubbing treatment), a WBUT of about 17 seconds after simulatedabrasion cycling treatment (i.e., equivalent to 30 cycles of digitalrubbing treatment), and no detectable polyquaternium-1 uptake. Nosurface cracking is observed.

Example 8

PAA-Coating Solution

A PAA coating solution is prepared by dissolving an amount of PAA (Mn:˜450 kDa, from Polysciences, Inc.) in a given volume of 1-propanol/water(10%/90% wt/wt) mixture to have a concentration of about 250 ppm and thepH is adjusted with formic acid (typically about 1.87 wt % in the finalsolution) to about 2.0.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

BTP+PG Dilution Buffer

Mix 1.95 gram of BTP, 15.25 gram of propylene glycol (PG) and 300 gramof Di-water until homogeneous. Add about 1.75 gram of 5N HCl and allowfor about 30 minutes of mixing. Adjust the pH to 7.4±0.1 using 5N HCl.

Preparation of BTP Solutions

Bis-tris propane solution is prepared by dissolving 0.14 gram of BTP in100 gram of DI (or distilled) water. No pH adjustment needed.

Preparation of Aqueous Polyaziridine Solution

PZ-28 solutions having a PZ-28 concentration of 0.2 wt % or 0.3 wt % areprepared by simply adding PZ-28 into the DI-water and no pH adjustment.

Preparation of Poly(MPC-co-AEM) (96/4 wt/wt)

Poly(2-methacryloyloxyethylphosphorylcholine-co-2-Aminoethylmethacrylate)(96/4 w/w) (i.e.,poly(MPC-co-AEM) is prepared according to the procedure described inExample 6.

IPC-10 Saline

IPC-10 saline is prepared as follows. Mix 74.3 w/w % poly(MPC-co-AEM)aqueous solution prepared above, 6.0 w/w % PAE, and 19.7 w/w % of BTPsolution. Adjust pH to 8±0.1 by 1N NaOH. React the mixture in a waterbath at temperature=70° C. for 4 hours. Remove the mixture from waterbath and cool down in a room temperature water bath. Dilute the mixturewith BTP+PG Dilution buffer in 1 to 4 ratio (1 part of reaction mixtureand 4 parts of BTP+PG dilution buffer) by weight and adjust pH to7.4±0.1. Filter the mixture by 5 μm filter capsules (Satorius item #:5051342P5-00-B) into sterile bottles and store them in refrigerator.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with IPA twice (the 1^(st) one for 30 minutes and the2^(nd) one for 150 minutes) for lens extraction, dipped in a IPA/watermixture at 50/50 volume ratio for about 30 minutes, dip-coated in thePAA coating solution prepared above for about 20 minutes, rinsed with PBtwice each for about 30 minutes, and then are packaged/sealed inpolypropylene lens packaging shells (blisters) with 0.6 mL of a mixtureof PZ-28 solution and IPC-10 saline prepared above (0.3 mL of IPC-10 isadded prior to inserting the lens, then 0.3 mL of the PZ-28 solution isadded and then mixed after sealed). The sealed lens packages are staged(i.e., left standing in an oven) at a temperature lower than 120° C. fora time period specified in Table 7. After the staging, the sealed lenspackages are autoclaved for about 45 minutes at about 121° C., formingSiHy contact lenses with a cross-linked hydrophilic coating (i.e., ahydrogel coating) thereon. The coating uniformity or intactness istested by Sudan black dye testing and the coating passed Sudan black dyetesting.

Table 7 reports some properties of the resultant water gradient SiHycontact lenses.

TABLE 7 [PZ-28] in Friction Cracking - Cracking - Staging packaging solPU rating* Invert folded At RT for 1 hr 0.1 wt % ≤0 0.5 0, 0, 0 0, 0, 0At RT for 1 hr 0.15 wt % ≤0 0, 0, 0 0, 0, 0 At RT for 2 hrs 0.1 wt % ≤00, 0, 0 0, 0, 0 At RT for 2 hrs 0.15 wt % ≤0 0, 0, 0 0, 0, 0 At 40° C.in 0.1 wt % ≤0 0.8 0, 0, 0 0, 0, 0 oven for 1 hr At 40° C. in 0.15 wt %≤0 0, 0, 0 0, 0, 0 oven for 1 hr At 40° C. in 0.1 wt % ≤0 0, 0, 0 0, 0,0 oven for 2 hrs At 40° C. in 0.15 wt % ≤0 0, 0, 0 0, 0, 0 oven for 2hrs *Determined after simulated abrasion cycling treatment (i.e.,equivalent to 30 cycles of digital rubbing treatment).

Example 9

PMAA-Coating Solution

A PMAA coating solution is prepared by dissolving an amount of PMAA (Mn:˜644 kDa, from PolyMaterials, Inc.) in a water/isopropanol (IPA) mixture(48.1 wt % IPA/50 wt % water) to have a concentration of about 600 ppmand the pH is adjusted with formic acid (typically about 1.87 wt % inthe final solution) to about 2.0.

Phosphate Buffered Saline (PBS)

PBS is prepared according to the procedures described in Example 3.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

Preparation of Poly(MPC-co-AEM) (96/4 wt/wt)

Poly(2-methacryloyloxyethylphosphorylcholine-co-2-Aminoethylmethacrylate)(96/4 w/w) (i.e.,poly(MPC-co-AEM) is prepared according to the procedure described inExample 6.

IPC-11 Saline

The reaction mixture of IPC-11 saline is prepared the same as describedin Example 6 for IPC-7. Dilute the mixture 5 times (i.e., 1 part ofreaction mixture with 4 parts of phosphate buffer by weight) with aphosphate buffer (˜33 mM of phosphate sodium salts and 0.77 wt % NaCl)and add 0.15 wt % of sodium citrate dihydrate. Finally, adjust pH to˜7.3. Filter the mixture by 0.22 μm PES sterile filter unit.

IPC-12 Saline

Same reaction mixture except replacing PBS by PB as described in IPC-11is prepared and reaction time=5 hrs. Same amount of sodium citratedihydrate, pH adjustment, and sterile filtration.

IPC-13 saline

Same reaction mixture as described in IPC-2 except replacingMPC-containing copolymer with poly(MPC-co-AEM) prepared in Example 6.The dilution, adding sodium citrate dihydrate, pH adjustment, andsterile filtration are the same as shown in IPC-11.

IPC-14 saline

Same reaction mixture as described in IPC-13 except replacing PBS by PBfor the reaction. The dilution, adding sodium citrate dihydrate, pHadjustment, and sterile filtration are the same as shown in IPC-13 aswell.

Preparation of Aqueous Polyaziridine Solution

PZ-28 solutions having a PZ-28 concentration of 0.3 wt % or 0.4 wt % areprepared by simply adding PZ-28 into the DI-water and no pH adjustment.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with IPA twice (the 1′ one for 35 minutes and the2^(nd) one for 145 minutes) for lens extraction, dip-coated in the PMAAcoating solution prepared above for about 50 minutes, rinsed with PBtwice each for about 25 minutes, and then are packaged/sealed inpolypropylene lens packaging shells (blisters) with 0.6 mL of a mixtureof PZ-28 solution and various IPC salines prepared above (for example:0.3 mL of one of IPC-11 to IPC-14 is added prior to inserting the lens,then 0.3 mL of the PZ-28 solution (or water without PZ) is added andthen mixed after sealed). The sealed lens packages are staged (i.e.,left standing in an oven) at room temperature for about 4 hrs. After thestaging, the sealed lens packages are autoclaved for about 45 minutes atabout 121° C., forming SiHy contact lenses with a cross-linkedhydrophilic coating (i.e., a hydrogel coating) thereon.

Table 8 reports some properties of the resultant water gradient SiHycontact lenses.

TABLE 8 PU WBUT* Packaging solution (μg/lens) (sec) IPC-11, ([PZ] =0.15%) 0.05 ± 0.04 14 ± 4.5 IPC-12 ([PZ] = 0.15%) 0.01 ± 0.06 16 ± 3.3IPC-13 ([PZ] = 0.15%) 0.01 ± 0.0  18 ± 7.9 IPC-14 ([PZ] = 0.15%) 0.04 ±0.06 21 ± 9.2 IPC-14 ([PZ] = 0.20%) 0.04 ± 0.05 22 ± 4.1 *aftersimulated abrasion cycling treatment (i.e., equivalent to 30 cycles ofdigital rubbing treatment)

Example 10

Preparation of PAA Coating Solution

A PAA coating solution is prepared by adding adequate amount of PAA in awater-IPA mixtures (e.g., 50/50 or 90/10 w/w). After PAA is fullydissolved, the pH is adjusted by adding ˜1.8% formic acid to the PAAaqueous solution to about 2. The target concentration of PAA is about0.025% by weight. The prepared PAA coating solution is filtered toremove any particulate or foreign matter.

Phosphate Buffered Saline (PBS)

A phosphate buffered saline is prepared by dissolving NaH₂PO₄.H₂O,Na₂HPO₄.2H₂O, and in a given volume of purified water (distilled ordeionized) to have the following composition: ca. 0.22 w/w %NaH₂PO₄.H₂O, ca. 1.95 w/w/% Na₂HPO₄.2H₂O, and ca. 3.97 w/w % NaCl.

IPC Salines

The IPC-7 and IPC-8 salines prepared in Example 6 are used in thisexample.

The IPC-15 saline is prepared as follows. Mix 77.0 w/w %poly(MPC-co-AEM) aqueous solution prepared in Example 6, 6.7 w/w % PAE,and 16.3 w/w % of a phosphate buffer (about 128 mM of phosphate sodiumsalts and about 4 wt % NaCl) (the concentration of poly(MPC-co-AEM) andPAE are about 10 times of the final saline). Adjust pH to ˜7.3 by 1NNaOH. React the mixture in a water bath at temperature ˜70° C. for 3hours. Remove the mixture from water bath and cool down in a roomtemperature water bath. Dilute the mixture 10 times (i.e, 1 part ofreaction mixture and 9 parts of phosphate buffer) with a phosphatebuffer (˜33 mM of phosphate sodium salts and 0.77 wt % NaCl) and adjustpH to ˜7.3. Filter the mixture by 0.22 μm PES sterile filter unit.

The IPC-16 saline is prepared by adding 0.2 wt % of PZ-28 into theIPC-15 prepared above.

The IPC-17 saline is prepared by adding 0.2 wt % of PZ-28 into theIPC-10 prepared in Example 8.

PU Reduction by PZ of PAA-Coated SiHy Contact Lenses

After de-molding, dry SiHy contact lenses (prepared in Example 2) areextracted with isopropanol (IPA) for 180 minutes for lens extraction,are dip-coated in the PAA solution prepared above for about 5, & 10minutes, are rinsed with PB twice each for about 30 minutes. The lensesare then packaged with one of the IPC salines prepared above (eitherwith 0.2 wt % or without PZ-28). The Polyquaternium-1 uptake and SurfaceCracking results are summarized in the following table (Table 9):

TABLE 9 H₂O % in PAA PAA dip PU Surface Packaging saline diping sol.time (min) (μg/lens) Cracking* IPC-15 (without 50% 5 0.44 0, 0, 0 PZ-28)(control) IPC-16 (with 0.2 50% 5 0.23 0, 0, 0 wt % PZ-28) IPC-7 (without50% 10 1.00 3, 3, 3 PZ-28) (control) IPC-8 (with 0.2 50% 10 0.46 2, 3, 2wt % PZ-28) IPC-17 (with 0.2 90% 20 0.07 0, 0 wt % PZ-28) *inspectionresults of three lenses after finger rubbing.

Example 11

IPC-18 Saline (Preparation of 5×IPC):

The following ingredients are mixed at room temperature in a containerat the following concentrations: 7.5 wt % of poly(MPC-co-AEM)(96/4 w/w)prepared in Example 6, 1.58 wt % PAE and 0.03 wt % BTP and the rest DIwater. The final pH is adjusted using 5N HCl to 8±0.1. The mixture isleft in a bath at 70° C. for 4 hrs. After pre-reaction, they are cooledto room temperature and then diluted 5-fold using a dilution bufferconsisting of 0.61 wt % BTP, 4.8 wt % propylene glycol and the rest DIwater (pH adjusted to 7.4). This saline is filtered using 5 um capsulefilters from Sartorius and then stored in the refrigerator immediatelyuntil further use in packaging lenses. This prepared saline has a chargedensity of 3050±200 uEq/L when measured using the Cary 60 technique forresidual charge.

Examples 12

PMAA-Coating Solution

The PMAA coating solution prepared in Example 9 is used in this example.

BTP+PG Dilution Buffer

Mix 0.846 gram of BTP, 6.6 gram of propylene glycol (PG) and 300 gram ofDi-water until homogeneous. Add about 1.75 gram of 5N HCl and allow forabout 30 minutes of mixing. Adjust the pH to 7.4±0.1 using 5N HCl.

BTP+Glycerol Dilution Buffer

Mix 0.846 gram of BTP, 7.8 gram of glycerol and 300 gram of Di-wateruntil homogeneous. Add about 1.75 gram of 5N HCl and allow for about 30minutes of mixing. Adjust the pH to 7.4±0.1 using 5N HCl.

BTP+NaCl Dilution Buffer

Mix 0.846 gram of BTP, 2.55 gram of sodium chloride (NaCl) and 300 gramof Di-water until homogeneous. Add about 1.75 gram of 5N HCl and allowfor about 30 minutes of mixing. Adjust the pH to 7.4±0.1 using 5N HCl.

Preparation of BTP Solutions

Bis-tris propane solution prepared in Example 8 is used in this Example.

Preparation of Aqueous Polyaziridine Solution

PZ Solution I having a PZ-28 concentration of 0.24 wt % is prepared bysimply adding PZ-28 into the BTP+PG dilution buffer.

PZ Solution II having a PZ-28 concentration of 0.24 wt % is prepared bysimply adding PZ-28 into the BTP+glycerol dilution buffer.

PZ Solution III having a PZ-28 concentration of 0.24 wt % is prepared bysimply adding PZ-28 into the BTP+NaCl dilution buffer.

IPC Salines

The IPC-7 prepared in Example 6 is used in this example.

The IPC-19 saline is prepared by mixing the IPC-10 prepared in Example 8with DI water at 1:1 ratio.

The IPC-20 saline is prepared by mixing the IPC-10 (also useBTP+glycerol to dilute the reaction mixture for IPC-10 afterpre-reaction) prepared in Example 8 with BTP+glycerol dilution buffer at1:1 ratio.

The IPC-21 saline is prepared by mixing the IPC-10 (also use BTP+PGdilution buffer prepared earlier in this example to dilute the reactionmixture for IPC-10 after pre-reaction) prepared in Example 8 with the PZSolution I prepared above at 1:1 ratio.

The IPC-22 saline is prepared by mixing the IPC-10 (also useBTP+glycerol to dilute the reaction mixture for IPC-10 afterpre-reaction) prepared in Example 8 with the PZ Solution II preparedabove at 1:1 ratio.

The IPC-23 saline is prepared by mixing the IPC-10 (also use BTP+NaCl todilute the reaction mixture for IPC-10 after pre-reaction) prepared inExample 8 with the PZ Solution III prepared above at 1:1 ratio.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with IPA twice (the 1^(st) one for 30 minutes and the2^(nd) one for 150 minutes) for lens extraction, dipped in a IPA/watermixture at 50/50 volume ratio for about 30 minutes, dip-coated in thePMAA coating solution prepared above for about 20 minutes, rinsed withPB twice each for about 30 minutes, and then are packaged/sealed inpolypropylene lens packaging shells (blisters) with 0.6 mL of a mixtureof a PZ solution and an IPC saline prepared above (0.3 mL of the IPCsaline is added prior to inserting the lens, then 0.3 mL of the PZsolution is added and then mixed after sealed). The sealed lens packagesare autoclaved at 121° C. for one autoclave cycle (45 minutes), for 5autoclave cycle (225 minutes), for 10 autoclave cycle (450 minutes), andfor 15 autoclave cycle (675 minutes) respectively. The multipleautoclave cycles are intended to determine the thermal stability (orshelf life of SiHy lenses) at an accelerated shelf life study. The lensdimensions of the resultant lenses are measured and reported in Table10.

Table 10 shows that: when the packaging solution is phosphate based, thediameter and BCE (base curvature equivalent) are increased as autoclavecycle number is increased; when the packaging solution is BTP based, thediameters or BCEs are decreased slightly or with minimal change asautoclave cycle number is increased. This indicates that BTP buffer maystabilize silicone hydrogel contact lens dimension/metro over shelflife.

TABLE 10 IPC Autoclave Lens dimensions Saline used Cycles Diameter (mm)BCE (mm) IPC-7 1 14.19 ± 0.02 8.23 ± 0.05 5 14.25 ± 0.02 8.27 ± 0.04 1014.27 ± 0.01 8.28 ± 0.03 15 14.32 ± 0.02 8.32 ± 0.04 IPC-19 1 14.17 ±0.02 8.21 ± 0.04 5 14.14 ± 0.01 8.20 ± 0.04 10 14.10 ± 0.03 8.15 ± 0.0415 14.11 ± 0.02 8.27 ± 0.05 IPC-21 1 14.19 ± 0.02 8.24 ± 0.05 5 14.16 ±0.02 8.20 ± 0.05 10 14.11 ± 0.02 8.18 ± 0.04 15 14.13 ± 0.03 8.23 ± 0.05IPC-22 1 14.17 ± 0.01 8.23 ± 0.04 5 14.16 ± 0.03 8.20 ± 0.03 10 14.10 ±0.02 8.16 ± 0.03 15 14.11 ± 0.02 8.16 ± 0.03 IPC-23 1 14.16 ± 0.02 8.20± 0.07 5 14.15 ± 0.01 8.22 ± 0.03 10 14.10 ± 0.01 8.20 ± 0.06 15 14.12 ±0.01 8.19 ± 0.05

Example 13

PMAA-Coating Solution

A PMAA coating solution is prepared by dissolving an amount of PMAA (Mn:˜644 kDa, from PolyMaterials, Inc.) in a water/isopropanol (IPA) mixture(48.1 wt % IPA/50 wt % water) to have a concentration of about 600 ppmand the pH is adjusted with formic acid (typically about 1.87 wt % inthe final solution) to about 2.0.

Another PMAA coating solution is prepared by dissolving an amount ofPMAA (Mn: ˜644 kDa, from PolyMaterials, Inc.) in a water/n-propanol(PrOH) mixture (48.1 wt % PrOH/50 wt % water) to have a concentration ofabout 600 ppm and the pH is adjusted with formic acid (typically about1.87 wt % in the final solution) to about 2.0.

Phosphate Buffered Saline (PBS)

PBS is prepared according to the procedures described in Example 3.

Phosphate Buffered (PB) without NaCl (PB, No NaCl)

PB is prepared according to the procedures described in Example 3.

IPC-14 Saline

The IPC-14 saline prepared in Example 9 is used in this example.

Preparation of Aqueous Polyaziridine Solution

PZ-28 solutions having a PZ-28 concentration of 0.3 wt % are prepared bysimply adding PZ-28 into the DI-water and no pH adjustment.

Water Gradient SiHy Contact Lenses

After de-molding, cast-molded SiHy contact lenses (prepared in Example2) are extracted with IPA thrice (the 1^(st) one for 40 minutes, 2^(nd)one for 115 minutes and 3^(rd) one for 25 minutes) for lens extraction,dip-coated in the PMAA coating solution prepared above for about 55minutes, rinsed with PB twice each for about 25 minutes, and then arepackaged/sealed in polypropylene lens packaging shells (blisters) with0.6 mL of a mixture of PZ-28 solution and IPC-14 saline prepared above(for example: 0.3 mL of IPC-14 is added prior to inserting the lens,then 0.3 mL of the PZ-28 solution is added and then mixed after sealed).The sealed lens packages are staged at room temperature for about 4 hrs.After the staging, the sealed lens packages are autoclaved for about 45minutes at about 121° C., forming SiHy contact lenses with across-linked hydrophilic coating (i.e., a hydrogel coating) thereon. Thesame coating solution is re-used another 2 more times with fresh IPA andlenses coated and prepared according to the procedure above describingfor the fresh IPA coating solution.

Another set of lenses were processed using n-Propanol (PrOH) as theextraction solvent and using PMAA coating solution prepared using PrOH.In addition, the coating solution is re-used twice as described aboveand lenses prepared according to procedure above.

Some of the key properties of the resultant water gradient SiHy contactlenses are summarized below (Table 11). The results demonstrate re-useof the coating solution at least three times when done from IPA or PrOHas the extraction and coating solution solvent. All the lenses exhibitexcellent long-lasting lubricity after cycling with a heavy cycler for14× using Renu as the lens care solution. The WBUT measurement resultsafter simulated abrasion cycling treatment (equivalent to 30 cycles ofdigital rubbing treatment) and also Sudan Black staining of lenses aftersimulated abrasion cycling treatment (equivalent to 30 cycles of digitalrubbing treatment) (results not shown) also further corroborate thisfinding.

TABLE 11 PU WBUT* Avg. Finger Lubricity Coating Details (μg/lens) (sec)after 14x cycling Fresh PrOH 0.04 ± 0.02 0.5 coating soln PrOH coating0.06 ± 0.04 16 ± 4 1 soln re-use #1 PrOH coating 0.08 ± 0.03 15 ± 2 —soln re-use #2 Fresh IPA 0.04 ± 0.03 21 ± 3 0.5 coating soln IPA coating0.05 ± 0.02 18 ± 2 1 soln re-use #1 IPA coating 0.05 ± 0.04 12 ± 2 —soln re-use #2 *after simulated abrasion cycling treatment (i.e.,equivalent to 30 cycles of digital rubbing treatment)

Example 14

Preparation of Water Gradient SiHy Contact Lenses

SiHy contact lenses with a PAA base coating thereon are preparedaccording to the procedures described in Example 19 of U.S. Pat. No.8,480,227 (herein incorporated by reference in its entirety), are usedin this example. The resultant PAA-coated SiHy contact lenses have awater content of about 32% by weight, an oxygen permeability of about146 barrers, a bulk elastic modulus of about 0.76 MPa, and a relativeion permeability of about 6 (relative to Alsacon lens). The PAA-coatedSiHy contact lenses are individually packaged/sealed in polypropylenelens packaging shells (blisters) with about 0.55 mL of the IPC-8 salineprepared in Example 6. The sealed lens packages are autoclaved for about45 minutes at about 121° C., forming SiHy contact lenses with across-linked hydrophilic coating (i.e., a hydrogel coating) thereon. Thecoating uniformity or intactness is tested by Sudan black dye testingand the coating passed Sudan black dye testing. The resultant watergradient SiHy contact lenses has a friction rating of 0; a WBUT of about28 seconds as measured with lenses directly out of package, a WBUT ofabout 20 seconds as measured with lenses after simulated abrasioncycling treatment (i.e., equivalent to 30 cycles of digital rubbingtreatment); and an average PU of about 0.06 μg/lens.

All the publications, patents, and patent application publications,which have been cited herein above in this application, are herebyincorporated by reference in their entireties.

What is claimed is:
 1. A process for producing a contact lens,comprising the steps of: (a) obtaining a contact lens precursor which isa coated contact lens which comprises a lens bulk material completelycovered with an anchor layer of a polyanionic polymer which comprises atleast 60% by mole of repeating units of at least one carboxyl-containingvinylic monomer; and (b) heating, in the presence of at least one firstpolyaziridine which has a number average molecular weight of about 2000Dalton or less and at least two aziridine groups, the contact lensprecursor in a first aqueous solution which comprises athermally-crosslinkable hydrophilic polymeric material which hasthermally-crosslinkable groups, to and at a temperature from about 30°C. to about 140° C. for a period of time sufficient to obtain thecontact lens, wherein the contact lens comprise (i) a crosslink anchorlayer thereon and (2) an outer surface hydrogel layer which iscovalently attached to the crosslinked anchor layer, wherein thecrosslinked anchor layer is obtained crosslinking the polyanionicpolymer in the anchor layer via crosslinkers derived from said at leastone polyaziridine in coupling reaction between at least two pair ofaziridine and carboxyl groups, wherein the outer surface hydrogel layeris formed by crosslinking the thermally-crosslinked hydrophilicpolymeric material, wherein the contact lens has a polyquaternium-1uptake (“PU_(pz)”) of about 0.6 μg/lens or less.
 2. The process of claim1, further comprising a step of soaking the contact lens precursor in asecond aqueous solution comprising at least one second polyaziridinehaving a number average molecular weight of about 2000 Dalton or lessand at least two aziridine groups.
 3. The process of claim 2, whereinthe first aqueous solution further comprises said at least one firstpolyaziridine.
 4. The process of claim 3, wherein the first and secondpolyaziridines independent of each other are selected from a groupconsisting of trimethylolpropane tris(2-methyl-1-aziridinepropionate),pentaerythritol tris[3-(1-aziridinyl)propionate], trimethylolpropanetris(3-aziridinopropionate), a Michael reaction product of a vinyliccrosslinker having at least three (meth)acryloyl groups and2-methylaziridine, a Michael reaction product of a vinylic crosslinkerhaving at least three (meth)acryloyl groups and aziridine, or acombination thereof.
 5. The process of claim 4, wherein the vinyliccrosslinker is selected from the group consisting of trimethylolpropanetriacrylate, pentaerythritol triacrylate,tris(2-hydroxyethyl)isocyanurate triacrylate, trimethylolpropaneethoxylate triacrylates, glyceryl propoxylate triacrylate,trimethylolpropane propoxylate triacrylates, pentaerythritoltetraacrylate, ditrimethylolpropane tetraacrylate, pentaerythritolethoxylate tetraacrylate, dipentaerythritol pentaacrylate, caprolactonemodified dipentaerythritol hexaacrylates, caprolactone modifieddipentaerythritol pentaacrylate, ethoxylated glycerol triacrylate,ethoxylated trimethylolpropane trimethacrylate, propoxylatedtrimethylolpropane trimethacrylate, ethoxylated pentaerythritoltrimethacrylate, ethoxylated pentaerythritol tetramethacrylate,ethoxylated dipentaerythritol trimethacrylate, ethoxylateddipentaerythritol tetramethacrylate, ethoxylated dipentaerythritolpentamethacrylate, ethoxylated dipentaerythritol hexamethacrylate,ethoxylated dipentaerythritol triacrylate, ethoxylated dipentaerythritoltetraacrylate, ethoxylated dipentaerythritol pentaacrylate, ethoxylateddipentaerythritol hexaacrylate, propoxylated pentaerythritoltrimethacrylate, propoxylated pentaerythritol triacrylate, propoxylatedpentaerythritol tetramethacrylate, propoxylated pentaerythritoltetraacrylate, propoxylated dipentaerythritol trimethacrylate,propoxylated dipentaerythritol tetramethacrylate, propoxylateddipentaerythritol pentamethacrylate, propoxylated dipentaerythritolhexamethacrylate, propoxylated dipentaerythritol triacrylate,propoxylated dipentaerythritol tetraacrylate, propoxylateddipentaerythritol pentaacrylate and propoxylated dipentaerythritolhexaacrylate, ethoxylated trimethyloylpropane triacrylamide, andcombinations thereof.
 6. The process of claim 5, wherein the first andsecond aqueous solutions independent of each other comprise twopolyaziridines, a first polyaziridine having at least two aziridinegroups of

and a second polyaziridine having at least two aziridine groups of

and at least one hydrophilic moiety selected from the group consistingof —OH, —[OC₂H₄O]_(n1)—. —CONHR¹, —CONR¹—, and combinations thereof,wherein n1 is an integer of 1 to 10 and R¹ is hydrogen, methyl or ethyl.7. The process of claim 6, wherein the first and second aqueoussolutions independent of each other comprise from about 0.01% to about2.5% by weight of said at least one first or second polyaziridine. 8.The process of claim 6, wherein the first aqueous solution is a lenspackaging solution, wherein the step of heating is performed byautoclaving the contact lens precursor immersed in the lens packagingsolution in a sealed lens package at a temperature of from about 115° C.to about 125° C. for approximately 20-90 minutes.
 9. The process ofclaim 8, wherein the lens packaging solution further comprises apartially hydrolyzed polyvinyl alcohol having a hydrolysis degree ofhydrolysis of from about 80% to about 98%.
 10. The process of claim 8,wherein the lens packaging solution has a pH of from about 7.0 to about9.0 before autoclaving and a pH of from about 6.5 to about 7.7 afterautoclaving.
 11. The process of claim 8, wherein the first aqueoussolution is obtained directly in the lens package by mixing a thirdaqueous solution and a fourth aqueous, wherein the third aqueoussolution comprises the thermally-crosslinkable hydrophilic polymericmaterial.
 12. The process of claim 11, wherein the third aqueoussolution is free of any polyaziridine.
 13. The process of claim 11,wherein the third aqueous solution further comprises said at least onepolyaziridine.
 14. The process of claim 11, wherein the fourth aqueoussolution comprises said at least one first polyaziridine.
 15. Theprocess of claim 11, wherein the fourth aqueous solution is free of anypolyaziridine.
 16. The process of claim 11, wherein said at least onecarboxyl-containing vinylic monomer is acrylic acid, methacrylic acid,ethylacrylic acid, 2-(meth)acrylamidoglycolic acid, and combinationsthereof.
 17. The process of claim 11, wherein the polyanionic polymer ispolyacrylic acid, polymethacrylic acid, poly(ethylacrylic acid),poly(acrylic acid-co-methacrylic acid), poly[ethylacrylicacid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid),poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylicacid-co-vinylpyrrolidone], poly[ethylacrylic acid-co-acrylamide],poly[ethylacrylic acid-co-vinylpyrrolidone], poly[(meth)acrylicacid-co-vinylacetate], poly[ethylacrylic acid-co-vinylacetate], orcombinations thereof.
 18. The process of claim 11, wherein thepolyanionic polymer is a graft polymer which is grafted onto the innerlayer or the lens bulk material, wherein the graft polymer comprisesrepeating units of at least one carboxyl-containing vinylic monomerwhich is acrylic acid, methacrylic acid, ethylacrylic acid,2-(meth)acrylamidoglycolic acid, and combinations thereof.
 19. Theprocess of claim 11, wherein the thermally-crosslinkable hydrophilicpolymeric material is a partially-crosslinked polymeric material thatcomprises a three-dimensional network and thermally-crosslinkable groupswithin the network or being attached to the network.
 20. The process ofclaim 19, wherein the thermally-crosslinkable hydrophilic polymericmaterial comprises azetidinium groups and is a partial reaction productof at least one azetidinium-containing polymer with at least onehydrophilicity-enhancing agent having at least one carboxyl, primaryamine, secondary amine, or thiol group.
 21. The process of claim 11,wherein the lens bulk material is a silicone hydrogel material, whereinthe silicone hydrogel bulk material comprises: (1) repeating units of atleast one polysiloxane vinylic monomer; (2) repeating units of at leastone hydrophilic vinylic monomer; (3) repeating units of at least onepolysiloxane vinylic crosslinker; (4) repeating units of at least onehydrophilic N-vinyl amide monomer; (5) repeating units of at least onepolycarbosiloxane vinylic monomer; (6) repeating units of at least onepolycarbosiloxane vinylic crosslinker; (7) repeating units of at leastone silicone-containing vinylic monomer having abis(trialkylsilyloxy)alkylsilyl or tris(trialkylsilyloxy)silyl group;(8) repeating units of one or more blending vinylic monomers; (9)repeating units of one or more non-silicone vinylic crosslinking agents;or (10) combinations thereof.
 22. The process of claim 11, wherein thelens bulk material is a non-silicone hydrogel material comprisingrepeating units of at least one hydroxyl-containing vinylic monomerselected from the group consisting of hydroxyethyl (meth)acrylate,glycerol (meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl(meth)acrylate, 3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl(meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl(meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide,N-tris(hydroxymethyl)methyl (meth)acrylamide, vinyl alcohol, allylalcohol, and combinations thereof.
 23. The process of claim 11, whereinthe lens bulk material comprise a central circular portion composed of arigid gas permeable lens material and an annular portion composed of anon-silicone hydrogel material surrounding the central circular portion,wherein the non-silicone hydrogel material comprises repeating units ofat least one hydroxyl-containing vinylic monomer selected from the groupconsisting of hydroxyethyl (meth)acrylate, glycerol (meth)acrylate,3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate,3-amino-2-hydroxypropyl (meth)acrylate, N-2-hydroxyethyl(meth)acrylamide, N-3-hydroxypropyl (meth)acrylamide, N-2-hydroxypropyl(meth)acrylamide, N-2,3-dihydroxypropyl (meth)acrylamide,N-tris(hydroxymethyl)methyl (meth)acrylamide, vinyl alcohol, allylalcohol, and combinations thereof.